Radial Access Systems and Methods for Delivery of Gas-Enrichment Therapy

ABSTRACT

Methods and systems for delivering gas-enriched blood within a vasculature of a patient may include providing a gas-enrichment system, the gas-enrichment system comprising a mixing chamber and a blood pump. The process may include inserting a catheter for drawing blood from the patient into a radial artery of the patient. The process may include drawing blood from the radial artery or from a vessel upstream of the radial artery at a blood flow rate without collapsing the artery or vessel to a degree that would substantially impede drawing blood. The process may include generating a gas-enriched blood by mixing the withdrawn blood with a gas-enriched liquid in a mixing chamber. The process may include delivering the gas-enriched blood to the vasculature of the patient.

CLAIM OF PRIORITY

This application claims priority under 35 U.S.C. § 119(e) to U.S. patentapplication Ser. No. 63/324,726, filed on Mar. 29, 2022, the entirecontents of which are hereby incorporated by reference.

TECHNICAL FIELD

The disclosure relates to systems and methods for the delivery ofgas-enriched blood into a patient.

BACKGROUND

Gas-enriched liquids are desirable in a wide variety of applications.However, at ambient pressure, the relatively low solubility of manygases, such as oxygen or nitrogen, within a liquid, such as water,produces a relatively low concentration of the dissolved gas in theliquid. One method of obtaining an increase in the gas concentrationlevel without significant increase in liquid volume involves aninjection and mixing of a gas-enriched liquid into a liquid of interest.A liquid can be gas-enriched at high pressure.

Conventional methods for the delivery of oxygenated blood oroxygen-enriched liquids to tissues and bodily liquids involve the use ofextracorporeal circuits for blood oxygenation. Extracorporeal circuitsrequire withdrawing blood from a patient, circulating the blood throughan oxygenator to increase blood oxygen concentration, and thendelivering the blood back to the patient.

SUMMARY

This document describes a gas-enrichment system configured to delivergas-enriched blood intravenously to a patient. The system for deliveringgas-enriched blood within the vasculature of a patient (hereinafter thedelivery system) is configured to connect to a catheter device todeliver the gas-enriched blood to the patient. The delivery systemincludes a blood circuit having a draw line and a return line. The drawline and return line are configured to connect to the catheter. Blood iswithdrawn from the patient via the draw line. The blood is mixed with agas-enriched liquid, or oxygen-enriched liquid such as a supersaturatedoxygen (SSO₂) enriched liquid, to create gas-enriched blood orsupersaturated oxygen (SSO2) enriched blood. The gas-enriched blood isdelivered back to the patient through the catheter via the return line,e.g., to provide localized delivery of gas enriched blood to ischemictissue in the patient. For example, SSO2 therapy may delivergas-enriched arterial blood directly to at-risk or ischemic myocardialtissue, increasing oxygen diffusion to the ischemic zone, therebyreducing endothelial swelling in the microvasculature and restoringmicrovascular flow

The delivery systems described herein are configured to delivergas-enriched liquid (e.g., gas-enriched blood) to the vasculature of thepatient. The blood circuit may include a blood circuit in which acatheter connected to a blood draw line is inserted into a radialartery, providing radial access to the vasculature, such that blood isdrawn from the radial vasculature (e.g., radial arteries) of the patientor other vessels via the radial vasculature. The delivery system isconfigured to allow blood draw from the radial artery and/or from avessel upstream of the radial artery in a precise and controlled mannerto avoid collapse of the radial artery or vessel upstream of the radialartery. The radial artery includes a blood vessel that supplies blood tothe forearm (lower part of the arm) and hand. The radial arterygenerally runs along a radial aspect of an anterior compartment of theforearm under the brachioradialis, lateral to the flexor carpi radialistendon. For the distal section of its course, the radial artery lies onthe surface of the radius. In certain implementations, the blood circuitmay include a bi-radial blood circuit in which a catheter connected to ablood draw line and a catheter connected to a blood return line are bothinserted into respective radial arteries of the patient, providingbi-radial access to the vasculature, such that blood is drawn from theradial artery or from another vessels upstream of the radial artery,e.g., brachial artery, axillary artery, or subclavian artery, via theradial vasculature and returned to the radial vasculature (e.g., radialarteries) or other vessels upstream of the radial artery, e.g.,brachial, axillary, or subclavian artery, of the patient.

The systems and methods described herein provide one or more advantages.The delivery system is configured to allow blood draw from the radialartery or other vessel upstream of the radial artery, e.g., brachial,axillary, or subclavian artery, in a precise and controlled manner toavoid collapse of the radial artery and/or other vessel upstream of theradial artery, e.g., brachial, axillary, or subclavian artery. Collapsemay refer to a crumpling or sagging of artery walls of the arterycausing blood flow blockage in the artery. In certain examples, collapseof an artery may refer to excessive flow causing high shear stress,which in turn causes vasospasm and abrupt closure (spasm) of the vessel.Though artery collapse can occur due to stenosis or other causes, in thecontext of SSO₂ therapy, collapse of the artery can occur due to lowinternal pressure in the artery responsive to a blood draw rateexceeding a threshold rate. The threshold flow rate is relatively smallin the radial artery relative to the aortal artery or subclavian artery,and therefore a maximum blood draw rate from the radial artery may belower than the aortal artery or subclavian artery.

The delivery systems described herein enable blood draw and returnthrough access points in the radial arteries. This allows localizedaccess to the vasculature of the patient (e.g., at the radial artery)without requiring insertion of catheters in other arteries or accessingother arteries of the patient (e.g., femoral artery, aorta, etc.). Thelocalized access to the vasculature simplifies the blood circuit. Forexample, using the radial artery to access the patient's vasculature canreduce bleeding compared to accessing the femoral artery. The simplifiedprocess can reduce a time to discharge of the patient compared to asystem that accesses the vasculature via the femoral artery or otherarteries away from the radial artery. The delivery system allows gasenrichment therapy such as SSO2 therapy to be performed without reducinga mobility of the patient because the femoral artery can be leftuntouched. The radial access to the vasculature of the patient reducesinfection rates and bleeding and is easier to access and easier to closewhen gas enrichment therapy such as SSO2 therapy is completed. Forexample, it's standard practice to provide access to the vasculature viathe radial artery for other procedures, such as angioplasty andpercutaneous Intervention (PCI), and such access can be performed byvarious caregivers, such as doctors and nurses, allowing of ease andconvenience of setup of the blood circuit for performing gas-enrichmenttherapy, such as SSO2 therapy.

In some implementations, the delivery system enables the draw line to beinserted into a radial vasculature of the patient and advanced to avessel upstream of the radial artery, e.g., the brachial, axillary, orsubclavian artery. The subclavian arteries includes a pair of largearteries in the thorax that supply blood to the thorax itself and thehead, neck, shoulder, and arms of the patient. Depending on the side ofthe body, the subclavian artery can have two origins: the aortic arch onthe left and the brachiocephalic trunk on the right. The draw linecatheter can be advanced into the subclavian artery to allow for alarger quantity of blood to be drawn from the patient at a faster drawflow rate (e.g., without collapsing the artery) compared to the radialartery. Advancing the draw line to the subclavian artery allows for drawline access through the radial artery and thus localized access to thevasculature of the patient without requiring access to the femoralartery, aorta, or other portion of the vasculature of the patient.

One or more of the advantages are enabled by one or more of thefollowing embodiments.

In a general aspect, a method for delivering gas-enriched blood within avasculature of a patient includes providing a gas-enrichment system, thegas-enrichment system comprising a mixing chamber and a blood pump. Themethod includes inserting a catheter for drawing blood from the patientinto a radial artery of the patient. The method includes drawing bloodfrom the radial artery or from a vessel upstream of the radial artery ata blood flow rate without collapsing the artery or vessel to a degreethat would substantially impede drawing blood. The method includesgenerating a gas-enriched blood by mixing the withdrawn blood with agas-enriched liquid in the mixing chamber. The method includesdelivering the gas-enriched blood to the vasculature of the patient.

In some implementations, the catheter is advanced to the vessel upstreamof the radial artery and the blood is drawn from the vessel upstream ofthe radial artery.

In some implementations, the blood flow rate is a predetermined bloodflow rate of 10-500 mL/min, 30-300 mL/min, or 50 -150 mL/min.

In some implementations, an inner diameter and length of the catheterare sufficient to support a predetermined blood flow rate of 50-150ml/min while avoiding a pressure drop that would cause pump cavitation.In some implementations, the inner diameter is 6-7 French, the length is10 to 100 cm and the pressure drop is from 0 mmHG to −100 mmHG.

In some implementations, inserting the catheter into a radial artery ofthe patient includes accessing a subclavian artery of the patientthrough the radial artery, and advancing the catheter into thesubclavian artery for drawing the blood from the subclavian artery.

In some implementations, inserting the catheter into the vasculature ofthe patient includes inserting a sheath into the vasculature of thepatient, the sheath configured to support the catheter in thevasculature of the patient, and inserting the catheter into the sheath.

In some implementations, the sheath comprises a braided wire and aplastic liner over the braided wire.

In some implementations, the sheath is between 50-100 centimeters inlength.

In some implementations, inserting the catheter into a radial artery ofthe patient includes advancing the catheter into the radial artery ofthe patient until distal band on the catheter aligns with apredetermined location in the vasculature of the patient.

In some implementations, the process includes controlling a draw rate ofthe catheter. The controlling includes determining a maximum draw ratebased on a size of the radial artery; determining a minimum draw rateand a draw pressure based on a pump flow requirement of a pumpconfigured to draw the blood from the radial artery; and controlling thedraw rate to be between the maximum draw rate and the minimum draw rate.

In some implementations, the maximum draw rate prevents controlling agiven draw rate causing a collapse of the radial artery, and wherein theminimum draw rate prevents controlling a given draw rate causingcavitation of the pump.

In some implementations, the draw rate is a function of a length of thecatheter.

In some implementations, the minimum draw rate is 100 milliliters (ml)per minute and wherein the draw pressure is at least 50 millimeters perMercury (mmHg).

In some implementations, the process includes measuring the draw rateusing a flow sensor; and generating an alert in response to measuring,by the flow sensor, that the draw rate is greater than the maximum drawrate or is less than the minimum draw rate.

In some implementations, the process includes measuring the drawpressure using a pressure sensor; and generating an alert in response tomeasuring, by the pressure sensor, that the draw pressure is greaterthan a maximum draw pressure.

In some implementations, one or more lumens of the catheter comprise abraided pattern.

In some implementations, the braided pattern comprises a rectangularcross section.

In some implementations, one or more lumens of the catheter eachcomprise a wall thickness between 0.005 inches to 0.015 inches, the wallthickness preventing kinking of the one or more lumens of the catheter.

In some implementations, one or more lumens of the catheter comprise anatraumatic tip.

In some implementations, the gas-enriched blood is formed in the mixingchamber by mixing the blood withdrawn from the patient with thegas-enriched liquid generated by a gas enrichment chamber.

In some implementations, the gas-enriched liquid comprises asupersaturated oxygen liquid. In some implementations, thesupersaturated oxygen liquid has an O₂ concentration of 0.1-6 ml O₂/mlliquid (STP).

In some implementations, the gas-enriched blood comprises asupersaturated oxygen enriched blood. In some implementations, thesupersaturated oxygen enriched blood comprises a supersaturated oxygenenriched blood having a pO2 of 600-1500 mmHg.

In some implementations, the process includes inserting a secondcatheter into a second radial artery of the patient for delivering thegas-enriched blood to the vasculature of the patient.

In some implementations, the process includes measuring a blood pressurein the radial artery or a vessel upstream of the radial artery using oneor more pressure sensors, wherein a controller of the gas-enrichmentsystem receives a signal from the one or more pressure sensors.

In some implementations, the controller generates an alert in responseto receiving a signal from the pressure sensor indicating a bloodpressure or change in blood pressure that exceeds a threshold or isbelow a threshold.

In some implementations, the controller controls a pump to adjust theblood draw flow rate in response to receiving a signal from the pressuresensor indicating a blood pressure or change in blood pressure thatexceeds a threshold or is below a threshold.

In some implementations, the vessel upstream of the radial artery is thebrachial, axillary, or subclavian artery.

In some implementations, drawing blood without collapsing the artery orvessel to a degree that would substantially impede drawing bloodcomprises preventing a collapse that would result in more than 5-10%reduction in cross-sectional area of an artery or vessel. In someimplementations, the catheter comprises a coiled lumen configured toprop open a vessel of the patient. In some implementations, the cathetercomprises a straight lumen. In some implementations, the cathetercomprises a coiled lumen configured to prop open a vessel of thepatient. In some implementations, the catheter comprises a straightconfiguration upon insertion and assumes a coiled configuration insidethe artery or vessel.

In a general aspect, a system for delivering gas-enriched blood within avasculature of a patient includes a blood circuit. The blood circuitincludes a pump configured to circulate blood in the blood circuit; amixing chamber configured to mix blood of the patient with agas-enriched liquid to form a gas-enriched blood; a catheter; and a drawline coupled to the mixing chamber and configured to connect thecatheter to the mixing chamber. The catheter is configured to beinserted into a radial artery of the patient, the catheter comprisingone or more lumens configured to draw the blood from the radial arteryor from a vessel upstream of the radial artery at a blood flow ratewithout collapsing the artery or vessel to a degree that wouldsubstantially impede drawing blood and send the blood to the mixingchamber.

In some implementations, the catheter is advanced to the vessel upstreamof the radial artery and blood is drawn from the vessel upstream of theradial artery.

In some implementations, the blood flow rate is a predetermined bloodflow rate of 10-500 mL/min, 30-300 mL/min, or 50 -150 mL/min.

In some implementations, an inner diameter and length of the catheterare sufficient to support a predetermined blood flow rate of 50-150ml/min while avoiding a pressure drop that would cause pump cavitation.

In some implementations, the inner diameter is 6-7 French, the length is10 to 100 cm and the pressure drop is from 0 mmHG to negative 100 mmHG.

In some implementations, the catheter is configured for insertion into asubclavian artery of the patient through the second radial artery.

In some implementations, the one or more lumens of the catheter comprisea braided pattern.

In some implementations, the braided pattern comprises a rectangularcross section.

In some implementations, the one or more lumens of the catheter eachcomprise a wall thickness between 0.005 inches to 0.015 inches, the wallthickness preventing kinking of the one or more lumens of the catheter.

In some implementations, the one or more lumens of the catheter comprisean atraumatic tip.

In some implementations, the system includes a sheath configured forinserting into the radial artery of the patient, the sheath configuredto support the catheter in radial artery. In some implementations, thesheath comprises a braided wire and a plastic liner over the braidedwire. In some implementations, the sheath is between 50-100 centimetersin length.

In some implementations, the catheter comprises a distal band on adistal portion of the catheter, the distal band configured to align witha predetermined location in the radial artery of the patient.

In some implementations, the system includes one or more flow sensorsfor measuring the draw rate; and a controller configured to receive asignal from the one or more flow sensors, wherein the controller isconfigured to generate an alert in response to receiving a signal fromthe flow sensor indicating that the draw rate is greater than a maximumdraw rate or is less than a minimum draw rate.

In some implementations, the system includes one or more pressuresensors for measuring the blood pressure in the radial artery; and acontroller configured to receive a signal from the one or more pressuresensors, wherein the controller is configured to generate an alert inresponse to receiving a signal from the pressure sensor indicating thatthe blood pressure is greater than a maximum blood pressure or is lessthan a minimum blood pressure.

In some implementations, the system includes one or more pressuresensors for measuring a blood pressure in the radial artery or a vesselupstream of the radial artery; and a controller configured to receive asignal from the one or more pressure sensors.

In some implementations, the controller is configured to generate analert in response to receiving a signal from the pressure sensorindicating a blood pressure or change in blood pressure that exceeds athreshold or is below a threshold.

In some implementations, the controller is configured to control thepump to adjust the blood draw flow rate in response to receiving asignal from the pressure sensor indicating a blood pressure or change inblood pressure that exceeds a threshold or is below a threshold.

In some implementations, the vessel upstream of the radial artery is thebrachial, axillary, or subclavian artery.

In some implementations, drawing blood without collapsing the artery orvessel to a degree that would substantially impede drawing bloodcomprises preventing a collapse that would result in more than 5-10%reduction in cross-sectional area of an artery or vessel.

In some implementations, the catheter comprises a coiled lumenconfigured to prop open a vessel of the patient. In someimplementations, the catheter comprises a straight lumen. In someimplementations, the catheter comprises a coiled lumen configured toprop open a vessel of the patient. In some implementations, the cathetercomprises a straight configuration upon insertion and assumes a coiledconfiguration inside the artery or vessel.

In some implementations, the catheter comprises a straight lumen.

In a general aspect, a system for delivering gas-enriched blood within avasculature of a patient includes: a gas-enrichment system configured togenerate a gas-enriched liquid; a mixing chamber configured to generatea gas-enriched blood by mixing blood from the patient with agas-enriched liquid received from the gas-enrichment chamber; a firstcatheter coupled to the mixing chamber, the first catheter comprisingone or more lumens configured to receive the gas-enriched blood from themixing chamber, the first catheter configured to be inserted into afirst radial artery of a patient and deliver the gas-enriched blood tothe patient; a second catheter configured to be inserted into a secondradial artery of the patient, the second catheter comprising one or morelumens configured to draw blood from the radial artery of the patient orfrom a vessel upstream of the radial artery and to send the withdrawnblood to the mixing chamber; and a pump configured to cause the secondcatheter to draw the blood and configured to cause the first catheter todeliver the gas-enriched blood.

In some implementations, the blood flow rate is a predetermined bloodflow rate of 10-500 mL/min, 30-300 mL/min, or 50 -150 mL/min.

In some implementations, second catheter is configured to be advanced tothe vessel upstream of the radial artery and to draw the blood from thevessel upstream of the radial artery at a predetermine flow rate withoutcollapsing the artery or vessel to a degree that would substantiallyimpede drawing blood, wherein the predetermine blood flow rate is 50-150 mL/min.

In some implementations, an inner diameter and length of the catheterare configured to support a predetermined blood flow rate of 50 -100mL/min while preventing a pressure drop greater than a thresholdpressure drop causing pump cavitation.

In some implementations, the inner diameter is 6-7 French, the length is10-100 centimeters and the pressure drop is from 0 mmHG to negative 100mmHG

In some implementations, the one or more sensors are configured tomeasure one or more blood parameters, and wherein operation of the firstcatheter, the second catheter, or both the first catheter and the secondcatheter are controlled based on the measured one or more parameters.

In some implementations, the one or more sensors comprises a bloodpressure sensor, pO₂ sensor, SO₂ sensor, or a flow rate sensor.

In some implementations, the system includes a control system configuredto control operation of the first catheter, the second catheter, or boththe first catheter and the second catheter based on one or more signalsrepresenting the measured one or more parameters.

In some implementations, the control system is configured to: receiveone or more signals representative of the measured one or moreparameters from the one or more sensors; and based on the one or moresignals, adjust a speed of the pump to alter a flow rate or flowpressure of the blood.

In some implementations, the one or more sensors comprises a pressuremeasuring device operable to measure blood pressure of the withdrawnblood.

In some implementations, the pressure measuring device is a pressuretube inserted through a communicating lumen in the second catheter,which communicating lumen is in fluid communication with the secondradial artery of the patient, the pressure tube proximally connected toa pressure monitor.

In some implementations, the pressure measuring device is configured tomeasure blood pressure of the withdrawn blood in a draw line connectingthe second catheter to the pump.

In some implementations, the pressure measuring device is a manometermounted at a proximal end of the second catheter.

In some implementations, the system includes a control system configuredto: receive the one or more signals representative of the measured oneor more parameters from the one or more sensors, wherein the one or moreparameters include pO₂ in the blood of the patient; and based on the oneor more signals of the measured pO₂, adjust a concentration of oxygen inthe gas-enriched liquid.

In some implementations, adjusting the concentration of oxygen in thegas-enriched liquid includes: increasing the concentration of oxygen inan initial control phase; and gradually reducing concentration of oxygenin a subsequent control phase until the pO₂ is within a pO₂ targetrange.

In some implementations, the one or more parameters comprise one or moreof a blood pressure, pO₂, SO₂, and a flow rate of the blood of thepatient.

In some implementations, an IR sensor is used to measure SO₂ in theblood of the patient.

In some implementations, the gas-enriched liquid comprises asupersaturated oxygen liquid.

In some implementations, the supersaturated oxygen liquid has an O₂concentration of 0.1-6 ml O₂/ml liquid (STP). In some implementations,the second catheter is configured for insertion into a subclavian arteryof the patient through the radial artery.

In some implementations, the one or more lumens of the second cathetercomprise a braided pattern.

In some implementations, the braided pattern comprises a rectangularcross section.

In some implementations, the one or more lumens of the second cathetereach comprise a wall thickness between 0.005 inches to 0.015 inches, thewall thickness preventing kinking of the one or more lumens of thesecond catheter.

In some implementations, the one or more lumens of the second cathetercomprise an atraumatic tip.

In some implementations, the system includes a first sheath configuredfor inserting into the first radial artery of the patient, the firstsheath configured to support the first catheter in the first radialartery.

In some implementations, the first sheath comprises a braided wire and aplastic liner over the braided wire. In some implementations, the firstsheath is between 50-100 centimeters in length.

In some implementations, the system includes a second sheath configuredfor inserting into the second radial artery of the patient, the secondsheath configured to support the second catheter in the second radialartery of the patient.

In some implementations, the second sheath comprises a braided wire anda plastic liner over the braided wire. In some implementations, thesecond sheath is between 50-100 centimeters in length. In someimplementations, the second catheter comprises a distal band on a distalportion of the second catheter, the distal band configured to align witha predetermined location in the second radial artery of the patient.

In some implementations, the system includes one or more clamps orvalves for controlling draw of the blood from the patient and deliveryof blood to the patient.

In some implementations, the system includes a bubble trap configured toremove air from the gas-enriched blood prior to delivery of the blood tothe patient.

In some implementations, the second catheter is advanced to a vesselupstream of the radial artery and blood is drawn from the vesselupstream of the radial artery.

In some implementations, the system includes one or more flow sensorsfor measuring a draw rate; and a controller configured to receive asignal from the one or more flow sensors, wherein the controller isconfigured to generate an alert in response to receiving a signal fromthe flow sensor indicating that the draw rate is greater than a maximumdraw rate or is less than a minimum draw rate.

In some implementations, the system includes one or more pressuresensors for measuring blood pressure in the radial artery; and acontroller configured to receive a signal from the one or more pressuresensors, wherein the controller is configured to generate an alert inresponse to receiving a signal from the pressure sensor indicating thatthe blood pressure is greater than a maximum blood pressure or is lessthan a minimum blood pressure.

In some implementations, the system includes one or more pressuresensors for measuring a blood pressure in the radial artery or a vesselupstream of the radial artery; and a controller configured to receive asignal from the one or more pressure sensors.

In some implementations, the controller is configured to generate analert in response to receiving a signal from the pressure sensorindicating a blood pressure or change in blood pressure that exceeds athreshold or is below a threshold.

In some implementations, the controller is configured to control thepump to adjust the blood draw flow rate in response to receiving asignal from the pressure sensor indicating a blood pressure or change inblood pressure that exceeds a threshold or is below a threshold.

In some implementations, the vessel upstream of the radial artery is thebrachial, axillary, or subclavian artery.

In some implementations, the second catheter comprises a coiled lumenconfigured to prop open a vessel of the patient.

In some implementations, the second catheter comprises a straight lumen.

In some implementations, drawing blood without collapsing the artery orvessel to a degree that would substantially impede drawing bloodcomprises preventing a collapse that would result in more than 5-10%reduction in cross-sectional area of an artery or vessel wherein theblood flow rate is a predetermined blood flow rate of 10-500 mL/min,30-300 mL/min, or 50-150 mL/min.

In some implementations, drawing blood without collapsing the artery orvessel to a degree that would substantially impede drawing bloodcomprises preventing a reduction of blood flow over a thresholdpercentage of 10-15%.

In some implementations, the blood flow rate is a predetermined bloodflow rate of 10-500 mL/min and blood flow in an artery is not reduced bymore than a predefined threshold percentage of 10-15%.

In some implementations, a system is configured for drawing bloodwithout collapsing the artery or vessel to a degree that wouldsubstantially impede drawing blood comprises preventing a reduction ofblood flow over a threshold percentage of 10-15%.

In some implementations, a system is configured for drawing bloodwithout collapsing the artery or vessel to a degree that wouldsubstantially impede drawing blood comprises preventing a collapse thatwould result in more than 5-10% reduction in cross-sectional area of anartery or vessel wherein the blood flow rate is a predetermined bloodflow rate of 10-500 mL/min, 30-300 mL/min, or 50-150 mL/min

In general, an implementation described with respect to one aspect maybe provided in combination with another aspect. The details of one ormore embodiments are set forth in the accompanying drawings and thedescription. Other features and advantages will be apparent from thedescription and drawings, and from the claims.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a diagram of an example gas-enrichment system for deliveringgas-enriched blood within the vasculature of a patient.

FIG. 2A is a diagram of example catheters in the vasculature in thepatient for bi-radial access of the vasculature for each of the drawline and the return line of the gas-enrichment system of FIG. 1 .

FIG. 2B is a diagram of an example draw catheter in the vasculature inthe patient for radial access of the vasculature for the draw line ofthe gas-enrichment system of FIG. 1 , the draw catheter being advancedinto the subclavian artery.

FIG. 2C is a diagram of an example catheter in the vasculature in thepatient for radial access of the vasculature for the draw line of thegas-enrichment system of FIG. 1 , including a sheath.

FIG. 2D is a diagram of an example catheter in the vasculature in thepatient for radial access of the vasculature for both draw and returnlines of the gas-enrichment system of FIG. 1 .

FIG. 2E is a diagram of example catheters in the vasculature in thepatient for bi-radial access of the vasculature for each of the drawline and the return line of the gas-enrichment system of FIG. 1 .

FIGS. 3A-3B are diagrams of an example draw catheter for radial accessof the vasculature in the patient.

FIG. 4 is a diagram of a portion of the system of FIG. 1-3 including acartridge.

FIG. 5 shows a perspective view of the system of FIGS. 1-4 .

FIG. 6 shows a block diagram of a process for gas-enrichment therapy.

FIG. 7 shows an example computer system.

The drawings primarily are for illustrative purposes and are notintended to limit the scope of the inventive subject matter describedherein. The drawings are not necessarily to scale; in some instances,various aspects of the inventive subject matter disclosed herein may beshown exaggerated or enlarged in the drawings to facilitate anunderstanding of different features. In the drawings, like referencecharacters generally refer to like features (e.g., functionally similarand/or structurally similar elements).

DETAILED DESCRIPTION

The following disclosure describes systems and methods related to, andexample embodiments of, gas enrichment therapy or supersaturated oxygenor gas therapy systems, methods and components. The systems permitgas-enrichment therapy, e.g., supersaturated oxygen (SSO₂) therapy to beprovided to patients. The system may be controlled based on an analysisof one or more physiological parameters. SSO₂ therapy refers tominimally invasive procedures for enriching oxygen content of bloodthrough catheter-facilitated infusion of supersaturated oxygen-enrichedphysiological fluid (e.g., blood) or infusion of supersaturatedoxygen-enriched liquid, such as saline, directly into a patient's bloodvessel. These procedures generally are aimed at treating a patient whohas suffered an acute myocardial infarction (AMI), but can be used forother conditions, including, but not limited to, peripheral vasculardisease as well. When delivering gas-enriched liquid (e.g., gas-enrichedblood), a delivery system may moderate a draw rate from the vasculatureof the patient to avoid collapsing an artery of the patient. Thedelivery systems described herein are configured to access the patient'svasculature via the radial artery such that blood is drawn from theradial artery or from other vessels via the radial artery of the patientwithout substantially collapsing the radial artery and/or the othervessels to a degree that would substantially impede drawing blood.

In certain implementations, substantially impeding blood flow within thevessel (such as from collapsing the blood vessel) can include thefollowing. In an example, substantially impeding the blood flow of anartery (such as the radial artery) may include reducing blood flow overa threshold percentage, such as about 10-15% or about 15-25%. In someimplementations, substantially impeding blood flow may include reducingblood flow (including blood draw) in the vessel by over 50%. In someimplementations, substantially impeding blood flow may include reducingblood flow (including blood draw) in the vessel by at least about 10%.In some implementations, substantially impeding blood flow may includereducing blood flow (including blood draw) in the vessel such thatarterial spasm is detectable. In some implementations, a pressuresensor, flow sensor, or a combination thereof is included on thecatheters described herein or elsewhere in the blood circuit or a bloodvessel of the patient. The sensor is configured to generate feedbackfrom the blood circuit or the blood vessel to detect impeded blood flow.For example, a draw side pressure or flow sensor in the blood circuit orin the patient can be configured to detect an arterial spasm, which isindicative of impeded blood flow in the patient. An arterial spasmincludes shrinking or constricting of the artery in which blood flow isirregular or reduced, and in which blood flow drops or blood pressurefluctuates to reduce blood flow (e.g., more than about a 10% reductionor change in blood flow volume or rate). In some implementations,drawing blood without collapsing the artery or vessel to a degree thatwould substantially impede drawing blood comprises preventing a collapsethat would result in more than 5-10% reduction in cross-sectional areaof an artery or vessel, wherein the blood flow rate is a predeterminedblood flow rate of 10-500 mL/min, 30-300 mL/min, or 50-150 mL/min. Insome implementations, drawing blood without collapsing the artery orvessel to a degree that would substantially impede drawing bloodcomprises preventing a reduction of blood flow over a thresholdpercentage of about 10-15%. In some implementations, the blood flow rateis a predetermined blood flow rate of 10-500 mL/min and blood flow in anartery is not reduced by more than a predefined threshold percentage ofabout 10-15%. In some implementations, a system is configured fordrawing blood without collapsing the artery or vessel to a degree thatwould substantially impede drawing blood comprises preventing areduction of blood flow over a threshold percentage of about 10-15%.

As described previously, the delivery systems described herein may beconfigured to deliver gas-enriched liquid (e.g., gas-enriched blood) tothe radial or other vasculature of the patient. The blood circuit may bea biradial blood circuit in which blood is drawn from and returned tothe radial vasculature (e.g., radial arteries) and/or other vesselsupstream of the radial artery, e.g., brachial, axillary, or subclavianarteries of the patient. The delivery system is configured to allowblood draw from the radial artery or from other vessels via the radialartery in a precise and controlled manner to avoid collapse of theradial artery and/or the other vessels.

In some implementations, a draw line is inserted into a radialvasculature of the patient and advanced to a subclavian artery. Thesubclavian arteries include a pair of large arteries in the thorax thatsupply blood to the thorax itself and the head, neck, shoulder, and armsof the patient. Depending on the side of the body, the subclavian arterycan have two origins the aortic arch on the left and the brachiocephalictrunk on the right. The draw line catheter can be advanced to orinserted into the subclavian artery to allow for a larger quantity ofblood to be drawn from the patient at a faster draw rate (e.g., withoutcollapsing the artery).

In certain implementations, the delivery system described in thisdocument is configured to perform measurements of one or morephysiological parameters (such as blood flow or blood pressure or both)to determine how to adjust control of blood draw and/or delivery ofgas-enriched blood to the patient. Controlling gas-enrichment therapymay refer to a process of adjusting the delivery of gas-enriched bloodor liquid either to increase the amount delivered or decrease the amountdelivered over a period of time (e.g., several seconds to a severalminutes) or increase or decrease the time of delivery or to stop orstart delivery of the gas enriched blood or liquid, or to increase ordecrease the amount of gas dissolved in liquid, which is then mixed withblood, in a precisely controlled way. For example, controlling deliveryof the gas enriched blood or liquid can include titrating the deliveryof the gas-enriched blood or liquid. The delivery system may beconfigured for measuring the physiological parameters during delivery ofthe gas-enriched blood to control a first catheter attached to the drawline and a second catheter attached the return line.

In certain implementations, the delivery system is configured forreal-time control of blood draw or the delivery of the gas-enrichedblood (e.g., real-time control loop) for controlling the draw rate(e.g., pump speed) or the delivery of the gas-enriched blood or liquidto the patient using radial access to the patient. Real-time in thiscontext refers to an instant or nearly instant generation of a controlsignal in response to receiving data from one or more sensors incommunication with a controller of the delivery system. The controlsignal is generated with minimal delay, allowing for processinglatencies and/or communication latencies inherent to measuring thephysiological parameter values and processing the measured data.Real-time therefore refers to processing the measured parameter valuesas the data are received at the processor rather than storing themeasured values for use in processing at a later time. For example, thedelivery system can continually update a value in a sensor bufferrepresenting the most recent measurement of the physiological parameterthat is available to the controller for processing.

FIG. 1 is a diagram of an example gas-enrichment and delivery system 100for delivering gas-enriched blood within the vasculature of a patient.The delivery system 100 can enable enrichment of a bodily fluid (e.g.,blood) with a dissolved gas or gas-enriched liquid. As an example, thedelivery system 100 creates a gas-enriched blood by enriching apatient's blood with a gas-enriched liquid, e.g., oxygen enrichedliquid, in an extracorporeal gas-enrichment and control system includinga controller 102 and a cartridge 200. Gas-enriched blood, e.g., oxygenenriched blood or supersaturated oxygen (SSO₂) enriched blood, isdelivered to a patient 144, thereby increasing oxygen in the blood ofthe patient and diffusion of oxygen into tissue to treat ischemic(oxygen-deprived) tissue, e.g., in patients who have suffered amyocardial infarction.

In certain implementations, oxygen enriched liquid or solution, e.g.,supersaturated oxygen liquid or solution, may include liquid having adissolved O₂ concentration of 0.1 ml O2/ml liquid (STP) or greater or0.1-6 ml O2/ml liquid (STP) or 0.2-3 ml O2/ml liquid (STP) (e.g.,without clinically significant gas emboli). When such supersaturatedoxygen liquid or solution is mixed with blood, the resulting blood maybe referred to as supersaturated oxygen enriched blood. In certainimplementations, the system 100 may deliver an infusion ofsupersaturated oxygen enriched blood having an elevated pO₂ in a targetrange of 400 mmHg or greater or 600-1500 mmHg or 760-1200 mmHg or around1000 mmHg.

In one example, supersaturated oxygen enriched blood may have a pO2 of760-1500 mmHg when a source blood delivered to the gas enrichment systemfor mixing with a supersaturated oxygen liquid or solution has a minimumpO₂ of 80 mmHg, the blood flow rate is 50-150 ml/min, the SSO2 salineflow rate is 2-5 ml/min and the dissolved O₂ concentration in saline is0.2-3 ml O2/ml saline (STP).

In another example, where the source blood is below 80 mmHg, thetreatment objective may be to boost the blood pO2 to above 80 mmHg, sothe system 100 may deliver an infusion of supersaturated oxygen enrichedblood having a pO2 level of 80 mmHg or greater or 80-760 mmHg.

In certain implementations, the delivery system 100 is configured toperform real-time or near real-time measurements of the blood flow rateor pressure (e.g., the change in pressure over time) in the radialartery and/or other vessel upstream of the radial artery, e.g.,brachial, axillary, or subclavian artery, and use that feedbackregarding the blood flow rate or pressure in the radial artery and/orother vessel upstream of the radial artery, e.g., brachial, axillary, orsubclavian artery, to adjust a draw rate of blood from the patient(e.g., by adjusting pump speed) to avoid collapse of the radial arteryand/or other vessel upstream of the radial artery, e.g., brachial,axillary, or subclavian artery, of the patient to a degree that wouldsubstantially impede drawing blood. The delivery system 100 may includeone or more sensors for measuring blood flow in the patient, asdescribed in relation to FIGS. 2A-3 .

In certain implementations, the delivery system 100 may include one ormore pressure sensors for measuring a blood pressure in the radialartery, a vessel upstream of the radial artery and/or in the draw line.The delivery system may include a controller configured to receive asignal from the one or more pressure sensors. The controller may beconfigured to generate an alert in response to receiving a signal fromthe pressure sensor indicating a blood pressure or change in bloodpressure that exceeds a threshold or is below a threshold. Thecontroller may be configured to control the pump to adjust the blooddraw flow rate in response to receiving a signal from the pressuresensor indicating a blood pressure or change in blood pressure thatexceeds a threshold or is below a threshold.

The delivery system 100 is configured for controlling gas-enrichmenttherapy in a patient by enriching a liquid with gas to form agas-enriched liquid and to mix the gas-enriched liquid with blood toform gas-enriched blood. A pump 118, subsequently described in furtherdetail, is configured to pump blood to and from the gas-enrichmentsystem to and from the patient through a plurality of fluid conduitsfluidly coupled to the gas-enrichment system.

In certain implementations, at least one sensor (e.g., described inrelation to FIG. 1B) is configured to measure one or more physiologicalparameters. A controller 102 comprising a processor, a memory, andassociated circuitry is communicatively coupled to the at least onesensor. The processor is configured to receive one or more signalscorresponding to a measured value of the one or more physiologicalparameters (e.g., blood pressure or flow rate) from the at least onesensor. The controller 102 is configured to control, based on the valuesof blood pressure or blood flow rate in the vasculature of the patient,an alert or control signal for sending to the pump 118 for adjustingdelivery or draw of blood from the patient.

The blood circuit includes the blood mixing chamber of the cartridgethat receives blood from the patient 144 and where enrichment of theblood with gas-enriched liquid occurs. The blood circuit may alsoinclude an air trap 120 or bubble trap chamber. The blood mixing chamberand/or bubble trap 120 may include one or more level sensors 160, e.g.,ultrasound sensors, for detecting the presence or absence of liquid inthe respective chamber or trap. These sensors 160 may send signals forcontrolling the flow control mechanisms depending on the presence orabsence of liquid. The blood circuit also includes the tubing betweenand among these chambers. The blood circuit of the delivery system 100is connected to an intravenous catheter 136 which is insertable into thevasculature of a patient 144 to complete the blood circuit. Blood isremoved from the patient 144, drawn into the cartridge of the deliverysystem 100, mixed with gas-enriched liquid, e.g., oxygen-enrichedsaline, and returned to the patient. The chambers of the blood circuitmay include one or more chambers of the cartridge 200, the bubble trap120. A bubble detector 126 may also be provided for detecting airbubbles in the blood circuit.

In certain implementations, the delivery system 100 may include aconsole controller 102 cartridge housing 104, a user interface 132, apump 118, a power supply 114, and an oxygen valve 108 and associatedoxygen supply connector 110. The delivery system is configured toconnect to several consumable items that are used as a part of thedelivery system 100, including an oxygen bottle 112, fluid source 106(or saline bag 106), a cartridge 200 and the catheter 136.

The delivery system 100 further includes a draw line 124 for drawingblood from a draw catheter 142 through connector 138 a. As describedherein and specifically in relation to FIGS. 2A-2D, the draw catheter isinserted in the vasculature of the patient 144 through the radialartery. The draw line 124 may include a bubble trap chamber 120 and isconfigured to interface with a pump 118 and may be configured tointerface with a first flow control mechanism, e.g., a draw line flowcontrol mechanism 122 of the delivery system 100. Pressure transducers138 a-b may be located on either side of the pump 118 to measurepressure of blood flowing through the blood circuit, such as through thedraw line 124, through the return line 130, or through each of the drawline and the return line.

The draw line 124 is connected to the draw catheter 142. For example,the draw catheter can be a single-use consumable device that is usedonce before being discarded. The draw catheter 136 includes a lumen fordrawing blood from the patient 144. The draw line 124 may be connected(e.g., by connector 138 a) to the catheter 142 to draw blood from thepatient 144. In some implementations, the draw catheter 142, whichincludes a lumen for drawing blood from the patient may be insertedthrough a sheath 142 positioned in the patient's vasculature. In thisexample, the draw line 124 is connected to the catheter 142.

The draw catheter 142 is configured to draw blood from a radial arteryand/or from a vessel upstream of the radial artery, e.g., the brachial,axillary, or subclavian artery, of the patient 144. Generally, thedelivery system 100 is configured to draw at least 100 cubic centimeters(cc's) per minute or 100 ml/min of flow rate from the patient. Thedelivery system 100 draw pressure may be maintained within a range of 50to 100 mmHg. The blood draw line pressure is maintained in the draw line124 to avoid a pressure drop that is greater than a threshold pressuredrop value to avoid cavitation by the blood pump 118 in which airbubbles or air cavities are formed in the blood circuit. A length of thedraw catheter 142 is short enough to enable the draw pressure in thedraw line 124 from the radial artery and/or from a vessel upstream ofthe radial artery, e.g., the brachial, axillary, or subclavian artery tobe maintained above the threshold value to prevent the radial arteryand/or a vessel upstream of the radial artery, e.g., the brachial,axillary, or subclavian artery from collapsing due to low pressure inthe radial artery or other vessel. In some implementations, the cathetermay be sized and configured, such that the pressure drop from thecatheter to the pump does not exceed a threshold value in order toprevent cavitation. In some implementations, the draw catheter 142 islocated in the brachial or subclavian artery, which are of a largerdiameter than the radial artery. In some implementations, the drawcatheter 142 is located in the radial artery and has a length or othermechanism to prevent artery collapse that would to a degreesubstantially impede drawing blood or blood flow.

The delivery system 100 includes a return line 130 for returninggas-enriched blood to the catheter 136 in the patient 144. The returnline 130 may be connected through a bubble detector 126, and connectedto the catheter via a connector 138 b. The return line may be configuredto interface with a second flow control mechanism, e.g., a return lineflow control mechanism 128. A draw clamp or valve can be used to performthe functions of the draw flow control mechanism 122, and a return clampor valve can be used to perform the functions of the return flow controlmechanism 128. In some implementations, another mechanism forcontrolling or regulating flow of the blood in the blood circuit (e.g.,to prevent blood flow and/or flow of room air or air bubbles) can beused to perform the functions of the draw flow control mechanism 122 orreturn flow control mechanism 128.

A return catheter 136 is connectable to the delivery system 100. Forexample, the return catheter 136 can be a single-use consumable devicethat is used once before being discarded. The return catheter 136includes a lumen for delivering gas-enriched blood to the patient 144.The return line 130 may be connected (e.g., by connector 138 b) to thecatheter 136 to return blood to the patient 144. In someimplementations, the return catheter 136, which includes a lumen fordelivery of the gas-enriched blood to the patient may be insertedthrough a sheath 142 positioned in the patient's vasculature. In thisexample, the return line 130 is connected to the catheter 136. Here, thevasculature of the patient 144 is divided into two portions. For thedraw catheter 142, the vasculature is the radial vasculature and/orother vasculature upstream of the radial artery, e.g., the brachial,axillary, or subclavian artery 144 a of the patient. For the returncatheter 136, the vasculature includes radial or other vasculature 144b, such as femoral vasculature.

In certain implementations, the blood circuit the draw line 124 may beconnected (e.g., by connector 138 a) to a sheath 142 inserted into thepatient 144 for drawing blood from the patient 144. The sheath 142includes a lumen for drawing blood from the patient 144, and the drawline 124 is connected to the sheath 142.

In certain implementations, the catheter 142 may be used for drawingblood from the patient at a location different than the location of thereturn catheter 136. The delivery system 100 uses two separate catheters136, 142 to control each of delivery/return and draw of the blood fromthe patient 144. In some implementations and as subsequently described,the draw catheter 142 can be shaped to assist in preventing collapse orsubstantial collapse of the radial artery and/or a vessel upstream ofthe radial artery, e.g., the brachial, axillary, or subclavian artery ofthe patient to a degree that would impede or substantially impededrawing blood. In some implementations, the draw catheter 142 isinserted into the radial artery. In some implementations, the drawcatheter 142 is inserted into the subclavian artery of the patientthrough the radial artery. When the subclavian artery is used, the drawcatheter 142 can be larger and configured for greater draw of the bloodfrom the patient 144 into the blood circuit.

In other implementations, the draw or return catheter 142/136 mayinclude a second lumen for drawing blood from the patient 144 so that asheath is not used, and so the catheter 142/136 is configured for bothreturning and drawing blood from the patient 144. In this example, thedraw line 124 and the return line 130 are connected to the catheter 136.The delivery system 100 is configured for use with different types ofcatheters. In another example, the sheath 142 includes a first lumen forconnecting to the draw line 124 for, drawing blood from the patient 144and a second lumen for connecting to the return line 130 for returningblood to the patient.

Turning to FIGS. 2A-2D, radial placement of the draw and returncatheters 136, 142 are shown in the patient vasculature 400. Thecatheters 136, 142 are configured to operate for gas-enrichment therapy,e.g., SSO₂ treatment, as described in relation to the delivery system100 of FIG. 1 .

FIG. 2A shows an example vasculature 400 of the patient 144 of FIG. 1 .The draw line 124 is connected (e.g., via connector 138 a) to a drawcatheter 410 (e.g., draw catheter 142 of FIG. 1 ). The draw catheter 410is positioned in a radial artery 402 a of the patient 144. The drawcatheter 410 is sized to enable draw of a particular amount of blood(e.g., 100 mL/min) while enabling the blood pressure or change in bloodpressure in the radial artery 402 a to be maintained above or below athreshold value. While FIG. 2A shows an example of a catheter positionedin the radial artery for blood draw from the radial artery, in otherexamples a catheter may be sized and configured for advancement (viaradial artery access) into other vessels upstream of the radial artery,e.g., the brachial, axillary, or subclavian artery, to allow for draw ofa particular amount of blood (e.g., 100 mL/min) from those arterieswhile allowing the blood pressure or change in blood pressure in thosearteries to be maintained relative to a threshold value.

In certain implementations, the draw catheter 410 may include one ormore sensors 406 a. For example, the draw catheter may include a wire408 a that extends from a distal end of the catheter 410 into the radialartery 402 a or vessel upstream of the radial artery of the patient. Thewire 408 a may support a sensor module 406 a. The sensor module 406 acan include one or more sensors that are instances of a same type ofsensor or different types of sensors. In an example, each of the sensorsof module 406 a includes a pressure sensor configured to measure bloodpressure or a change in blood pressure in the radial artery 402 a of thepatient. Two pressure sensors can provide a pressure differential (Δp)value for a region of the radial artery 402 a. The wire 408 a isinserted into the radial artery 402 a and can record a blood pressure inthe radial artery 402 a. This can ensure that a minimum blood pressureis maintained in the radial artery 402 a to prevent collapse of theradial artery during blood draw from the radial artery. In someimplementations, the sensors module 406 a includes flow sensorsconfigured to measure the flow of blood directly in the radial artery408 a. The flow sensors can include temperature, electromagnetic,mechanical, or ultrasonic flow sensors. For example, a pressure sensoron the distal end of the wire can act as a distal thermistor, while apressure sensor on the proximal shaft of the wire serves as a proximalthermistor. Accordingly, a mean transit time (T_(mn)) ofroom-temperature saline injected into a coronary artery can bedetermined from a thermodilution curve. Using the thermodilutiontechnique, a correlation between the inverse of T_(mn) (1/_(Tmn)) andabsolute coronary flow is shown. Absolute coronary flow≈1/T_(mn). Insome implementations, a pressure sensor may measure a blood pressurechange over time, e.g., a blood pressure drop in the radial artery ordraw catheter, and provide feedback to ensure that the pressure dropdoes not exceed a threshold value, which would result in a vesselcollapsing to a degree that would substantially impede drawing blood. Incertain implementations, where the catheter is inserted into othervessels upstream of the radial artery, e.g., the brachial, axillary, orsubclavian artery, the sensors would be positioned in the respectivevessel and configured to measure blood pressure or blood pressure changeover time or a pressure differential for a region of the vessel or bloodflow rate in said vessel or draw catheter to prevent vessel collapse orcavitation.

In certain implementations, pressure and or flow may be measured andprovide feedback in order to prevent or reduce vessel collapse thatwould substantially impede blood flow or drawing of blood. For example,in certain arteries, the system may prevent a collapse resulting in morethan 5-10% reduction in cross-sectional area of an artery or vessel. Insome implementations, the sensors of the sensor module 406 a can detectarterial spasms, which can be indicative of impeded blood flow. Arterialspasms include shrinking or constricting of the artery in which bloodflow is irregular or reduced, and in which blood flow drops or bloodpressure fluctuates to reduce blood flow (e.g., by more than 10%). Incertain implementations, the senor module may include a flow and/orpressure sensor. In some implementations, the one or more sensors of thesensor modules 406 a-b can be positioned in either or both of the drawline or the return line. In some implementations, the one or moresensors of the sensor modules 406 a-b can be positioned in thevasculature of the patient, as shown in FIG. 2E. In someimplementations, the one or more sensors of the sensor modules 406 a-bcan be positioned in a combination of locations, such as in thevasculature of the patient, in either or both of the draw line andreturn line, and in the console of the delivery system 100.

In some implementations, the wire 408 a is positioned on or near adistal end of the draw catheter 410. In some implementations, the module406 a is positioned directly on the body of the catheter 410. The wire408 a can extend through a lumen of the catheter 410 out of the distalend of the catheter. In some implementations, the wire 408 a extendsalong the catheter 410 shaft on an exterior of a catheter lumen. In someimplementations, the wire 408 a is positioned on a separate probe thatis not directly attached to the draw catheter 410. In someimplementations, a second, separate catheter is used to support the oneor more sensors.

Similarly, a return catheter 412 (e.g., similar to return catheter 136of FIG. 1 ) is positioned in a radial artery 402 b of the patient 144and is connected to the blood circuit (e.g., via connector 138 b. In theexample shown in FIG. 2A, the draw catheter 410 is positioned in a firstradial artery 402 a of the patient, and the return catheter 412 ispositioned in a second radial artery 402 b of the patient in a differentarm of the patient. In some implementations, the draw catheter 410 andreturn catheter 412 are positioned in the same radial artery in the samearm. In certain implementations, the draw and return catheters may beinserted into the vasculature via a first and second sheath.

In certain implementations, the return catheter may include one or moresensors. For example, the return catheter 412 may include a wire 408 bthat extends from a distal end of the catheter 412 into the radialartery 402 b or vessel upstream of the radial artery of the patient. Thewire 408 b supports sensor module 406 b. The sensor module 406 b caninclude one or more sensors that are instances of a same type of sensoror different types of sensors. In an example, each of the sensors ofmodule 406 b includes a pressure sensor configured to measure bloodpressure in the radial artery 402 b of the patient. The two pressuresensors can provide a pressure differential (Δp) value for a region ofthe radial artery 402 b or a change in pressure over time. The wire 408b is inserted into the radial artery 402 b and can record a bloodpressure in the radial artery 402 b. In some implementations, thesensors module 406 b includes flow sensors configured to measure theflow of blood directly in the radial artery 408 ba. The flow sensors caninclude temperature, electromagnetic, mechanical, or ultrasonic flowsensors. In certain implementations, where the catheter is inserted intoother vessels upstream of the radial artery, e.g., the brachial,axillary, or subclavian artery, the sensors would be positioned in therespective vessel and measure pressure or flow therein.

In some implementations, the wire 408 b is positioned on or near adistal end of the return catheter 412. In some implementations, themodule 406 b is positioned directly on the body of the catheter 412. Thewire 408 b can extend through a lumen of the catheter 412 out of thedistal end of the catheter. In some implementations, the wire 408 bextends along the catheter 412 shaft on an exterior of a catheter lumen.In some implementations, the wire 408 b is positioned on a separateprobe that is not directly attached to the return catheter 412. In someimplementations, a second, separate catheter is used to support the oneor more sensors.

The sensor modules 406 a-b are each configured to send data to acontroller (e.g., controller 102 of FIG. 1 ) which can display feedbackon the user interface 132 responsive to receiving the data from thesensors. The feedback that is displayed on the user interface 132 caninclude a display of blood pressure values, blood flow rate values, arate of delivery of the gas-enriched blood (e.g., a titration value), apump speed and direction, and so forth. As subsequently described inadditional detail, the feedback displayed by the user interface 132 caninclude a time series showing a sequence of measurements. In someimplementations, the feedback can include a diagram or graph that iscontinually or intermittently updated as new data are acquired. Forexample, the pressure values can be graphed in relation to time.

The data from the sensor modules 406 a-b is sent to the controllereither automatically and directly or through action of a user. In someimplementations, the data are sent from sensor modules 406 a-b over thewire 408 a-b to the controller 102, which is connected either directlyto the wire or indirectly to the wire through a catheter hub (notshown).

Data generated from the sensors of the sensor modules 406 a-b are usedfor controlling delivery of the gas-enriched blood to the vasculature ofthe patient. The delivery system 100 is configured to control blood drawand gas-enriched blood delivery based on the feedback of the sensors ofsensor modules 406 a-b. In some implementations, the delivery system 100is configured to augment blood flow. In some implementations, thedelivery system 100 is configured to increase a concentration of oxygenin the gas-enriched liquid/blood delivered to the patient. In someimplementations, the delivery system 100 increases or decreases anamount of gas-enriched blood/liquid to the patient, either by increasingor decreasing the flow rate of blood draw or gas-enriched blood (e.g.,SSO₂) delivery or by increasing or decreasing the duration ofgas-enriched blood (e.g., SSO₂) delivery.

The control of the gas-enrichment therapy may be performed in real-timeor near-real time. The delivery of the gas-enriched blood to the patientmay not paused during measurement of the one or more physiologicalparameters. The measurement of the pressure or flow represents acontemporaneous status of the patient for the delivery of thegas-enriched blood to the patient. Generally, the real-time or near-realtime comprises processing, by the controller, data received from the oneor more sensors as soon as the data are available to the controller andgenerating the control signal based on the processing, as previouslydescribed.

The controller 102 is configured to control gas-enrichment (e.g., SSO2)delivery over time. The controller 102 receives one or more signalscorresponding to a measured value of the one or more physiologicalparameters from the sensor modules 406 a-b. The controller 102 canreceive a series of measured values of the pressure values or flowvalues from the sensors over time. The series of measured valuescorresponds to a period of time during delivery of the gas-enrichedblood to the patient. The controller 102 determines, based on the seriesof measured values, whether the value of the pressure or flow isincreasing or decreasing over time. The controller 102 generates thecontrol signal that is configured to increase or reduce the blood flowrate or amount of the gas-enriched blood delivered to the patient basedon the time series of values.

In certain implementations, if the blood pressure values in a patientare increasing over time, the controller may provide an alert or reducethe pump speed, thereby reducing blood flow rate and blood pressure. Forexample, if the pressure values are decreasing over time, the controllermay provide an alert or increase the pump speed, thereby increasingblood flow rate and blood pressure. If the pump speed and blood flowrate is modified, the SSO2 saline flow rate and/or the dissolved O2concentration in saline may also need to be modified to achieve adesired pO2 in blood. For example, supersaturated oxygen enriched bloodmay have a pO2 of 760-1500 mmHg when a source blood delivered to the gasenrichment system for mixing with a supersaturated oxygen liquid orsolution has a minimum pO₂ of 80 mmHg, the blood flow rate is 50-150ml/min, the SSO2 saline flow rate is 2-5 ml/min and the dissolved O₂concentration in saline is 0.2-3 ml O2/ml saline (STP), and suchparameters may be modified depending on changes to one or more of theother parameters. For example, if the blood flow rate is reduced, eitherthe SSO2 saline flow rate or dissolved O₂ concentration in saline couldbe reduced to maintain desired pO2 levels. Reducing oxygen pressure mayreduce both SSO2 saline flow rate and dissolved O₂ concentration insaline.

Generally, the controller 102 controls draw of the blood from the drawcatheter 410 to maintain a pressure in the blood circuit withoutdropping pressure in the radial artery, or other vessels upstream of theradial artery, e.g., the brachial, axillary, or subclavian artery 402 a,too low such that the blood vessel would collapse to a degree that wouldimpede or substantially impede blood flow or drawing blood. A catheter410 length may enable drawing blood from a region, e.g., at 100 mL/mindraw rate, without collapse to a degree that would substantially impedeblood flow or drawing blood (e.g., from the subclavian artery, as shownin relation to FIG. 2B).

In some implementations, a low pressure monitor, pressure sensor, isused at a connection of the draw line 124 to the draw catheter 410 orsheath (see FIG. 2C) or at the pump or at the distal end the catheter.The low pressure monitor is configured to measure pressures slightlyhigher than those required by the blood pump 118. For example, apressure of 50 mmHg or higher at a 100 mL/min flow rate may bemaintained to avoid cavitation and/or vessel collapse. The pressuremonitor could have an alarm setting for pressure drops of −50 to −100mmHg to protect the blood pump 118 from cavitation and/or generatealerts for momentary kinks in the draw line 124 or other flowrestrictions. An example of a pressure monitor includes an ICU MedicalTransPac IV transducer coupled to a GE CareScape™ monitor.

FIG. 2B shows an example vasculature 402 of the patient 144 of FIG. 1 .The draw line 124 is connected (e.g., via connector 138 a) to a drawcatheter 410 (e.g., the catheter may be introduced through a sheath, asdescribed in relation to FIG. 2C). The catheter 410 accesses thevasculature through a radial artery 402 of the patient 144 and isadvanced to the subclavian artery 404. The draw catheter 410 includes ahub 420 (which remains outside the vasculature). Hub 420 a can be for adraw catheter 410, and hub 420 b can be for a return catheter 412. Thedraw catheter 410 extends from the hub to a distal tip 422 of the drawcatheter 410. A wire 408 and sensor module 406 a-b may extend from thedistal tip 422 and can operate in a manner described in relation to FIG.2A. The draw catheter 410 is sized and configured to enable draw of aparticular amount of blood (e.g., 100 mL/min) while enabling the bloodpressure in the radial and/or subclavian arteries to be maintained abovea threshold value to prevent vessel collapse that would substantiallyimpede blood flow or drawing blood.

The draw catheter 410 is long enough to reach a subclavian artery 404form the radial artery 402, such as from an insertion point 418 from theexterior of the patient near the elbow of the patient 144. The distalend of the draw catheter 410 is positioned in a subclavian artery 404 ofthe patient 144. The draw catheter 410 is sized to enable draw of aparticular amount of blood (e.g., 100 mL/min) while enabling the bloodpressure in the subclavian artery 404 to be maintained above a thresholdvalue to prevent vessel collapse that would substantially impede bloodflow or drawing blood. The draw catheter 410 may extend to thesubclavian artery 404 at a length of up to approximately 60 centimeters.The draw catheter 410 extends to the subclavian artery 404 for drawingblood from the patient. In some implementations, the catheter 410 isless than 50 centimeters, and is used to reach from the radial artery402 to the subclavian artery 404.

FIG. 2C shows an example vasculature 402 of a patient 144. A draw line124 is connected (e.g., via connector 138 a) to a draw catheter 424(e.g., draw catheter 142 of FIG. 1 ). The draw catheter 424 extends froma catheter hub 420 (located outside of the vasculature) to a distal tip422. The draw catheter 424 may be introduced via a sheath 416. A wire408 and sensor module 406 may extend from the distal tip 422 and canoperate in a manner described in relation to FIG. 2A. In this example,the draw catheter 424 extends to the radial artery, rather than all theway to the subclavian artery 404. In other implementations, the cathetermay be inserted into other vessels upstream of the radial artery, e.g.,the brachial, axillary, or subclavian artery.

The draw catheter 424 is inserted into the radial vasculature 402through the sheath 416. The draw catheter 424 is advanced through thesheath 416 up to the catheter hub 420. In certain implementations, thesheath 416 may have a draw port connected to the draw line for drawingblood and the catheter 424 may serve as a return catheter for deliveringgas-enriched blood to the vasculature, e.g., to coronary artery. Thisconfiguration allows for a single insertion point 418 to be used on thepatient for both draw of the blood from the radial artery and/or othervessel downstream from the radial artery, e.g., subclavian artery, or acombination thereof and return of gas enriched blood to the vasculature,e.g., the coronary artery.

In some implementations, the catheters and/or the sheaths describedherein may include an armored body. The armored body includes braidedwire for flexibility and strength, with a medical grade plastic linerfor containment of the catheter and/or sheath. Generally, the catheterand/or sheath is kink resistant. To be kink resistant, the catheterand/or sheath includes a wall thickness of about 8-12 thousands of aninch. In some implementations, the wall thickness is between 0.005inches to 0.015 inches. In some implementations, the catheter and/orsheath includes an atraumatic tip such that there is a non-braidedtransition to the catheter or sheath tip. In some implementations, thedraw catheter or sheath and the return catheter or sheath are combinedinto a single hybrid catheter or sheath including at least two lumens: afirst lumen for drawing blood and a second, different lumen for retuninggas-enriched blood to the patient 144. For the hybrid catheter, anintroducer sheath may or may not be used at the access point 418.

In the example of FIG. 2D, the draw catheter 412 and the return catheter422 (shown in the subclavian, but may be advanced further upstream intoa coronary artery), are each positioned in the same arm of the patient144 such that both catheters access the vasculature via the radialartery 402 of the patient at insertion point 418. Optionally, thecatheters may be inserted through a sheath 416 in the radial artery.

As described previously, the return catheter 422 is configured to returngas-enriched blood to the patient 144. The draw catheter 412 isconfigured to draw blood from artery 404 of the patient for gasenrichment in the blood circuit described in relation to FIG. 1 . Inthis example, the access points for the catheters 424, 412 are the sameaccess point 418 for accessing the radial artery 402 of the patient 144.

To enable the draw catheter 412 and return catheter 424 to be in thesame arm of the patient 144, the return catheter 424 extends to thedistal tip 422 in a subclavian artery 424 of the patient. The drawcatheter 412 draws blood near the radial artery 402 of the patient. Incertain implementations, the draw catheter may be advanced to and drawblood from vessels upstream of the radial artery, e.g., the brachial,axillary, or subclavian artery.

Exemplary draw catheters, e.g., as shown in FIGS. 2A-2C are configuredfor use with the delivery system 100 of FIG. 1 . The draw catheters maybe configured for operating with the delivery system 100 such as drawcatheter 142. The draw catheters are configured to be inserted into theradial artery of the patient as previously described. In someimplementations, the draw catheters described herein are configured forinsertion or advancement into vessels upstream of the radial artery,e.g., the brachial, axillary, or subclavian artery, of the patientthrough the radial artery, as previously described.

Generally, an outer diameter and length of the catheters are sufficientto support a blood flow rate or predetermined blood flow rate of 50-150mL/min while avoiding a pressure drop that would cause pump cavitation.Example geometries of such catheters are shown in Table 1 below.

TABLE 1 Draw Pressure at Blood Pump based on guide catheter size andlength (100 ml/min flow rate) (assuming arterial pressure 80 mmHgnominal) Catheter 6 Fr Guide Draw 7 Fr Guide Draw Length (cm) Pressure(mmHg) Pressure (mmHg) 0 30 30 10 12 19 20 −7 8 30 −25 −3 40 −44 −14 50−62 −25 60 −81 −35 70 −99 −46 80 — −57 90 — −68 100 — −79

In some implementations, the catheter has an outer diameter that is 6-7French. The catheter length may be 10-100 cm. Depending on the length ofthe catheter, the pressure drop caused by blood draw at a rate of 100ml/min, from the distal end of the catheter to the blood pump, may bebetween 0 mmHG to negative 180 (−180) mmHG. In certain implementations,a pressure monitor may provide an alert of a presser drop from −50 to−100 mmHG.

The draw catheters described herein can each be configured as follows.In some implementations, the one or more lumens of the catheter cancomprise a braided pattern. In some implementations, the braided patterncomprises a rectangular cross section. Generally, the braid is flexiblebut is still firm to prevent kinking. Generally, the one or more lumensof the catheter each comprise a wall thickness between 0.005 inches to0.015 inches. The wall thickness prevents kinking of the one or morelumens of the catheter. In some implementations, the one or more lumensof the catheter comprise an atraumatic tip. An atraumatic tip includes ashape and material to cause minimal tissue injury. For example, theatraumatic tip can be rounded. The atraumatic tip can taper to a roundededge. The atraumatic tip can include a soft, pliable material that doesnot pierce the radial artery 402. In some implementations, the catheterincludes a distal band on a distal portion of the catheter. The distalband aligns with a predetermined location in the radial artery or avessel upstream of the radial artery, e.g., the brachial, axillary, orsubclavian artery of the patient to assist a user in determining how farto advance the catheter into the artery of the patient during use forproper positioning, e.g., either in the radial artery or near thesubclavian artery.

In some implementations, the catheter is supported by a sheathconfigured for inserting into the radial artery of the patient. Thesheath can include a braided wire and a plastic liner over the braidedwire. Generally, the braid is flexible but is still firm to preventkinking. The braid can include a wire that is encapsulated (e.g.,extruded or overmolded) with medical grade plastic (e.g. Pebax™).Generally, for the sheath, a flat braid provides a rectangular, thinnercross section relative to a round braid. A rounder braid causes arelatively thicker wall for the sheath. Generally the sheath is between˜50-100 centimeters in length.

FIG. 2E shows an example vasculature 400 of the patient 144 of FIG. 1 .The draw line 124 is connected (e.g., via connector 138 a) to a drawcatheter 410 (e.g., draw catheter 142 of FIG. 1 ). The draw catheter 410is inserted in a radial artery 402 a of the patient 144 and advanced toa subclavian artery 404 to draw blood at a subclavian artery 404. Thedraw catheter 410 is sized to enable draw of a particular amount ofblood (e.g., 100 mL/min) while enabling the blood pressure or change inblood pressure in the radial artery 402 a to be maintained above orbelow a threshold value. The blood circuit therefore includes drawingblood at the subclavian artery 404, as described in relation to FIG. 2D,and returning blood to the patient in a radial artery 402 b as describedin FIG. 2A. This combination of radial return and subclavian draw ofblood can help reduce the likelihood of collapsing the radial orsubclavian artery and substantially impeding blood flow.

FIGS. 3A-3B show an example catheter 500 configured to prop or hold opena radial vessel 402 of the patient. For example, in FIG. 3A, thecatheter 500 enters in a straight configuration. A shape memory of thecatheter 500 allows the catheter body 502 to coil once in thevasculature 402 to keep the vessel propped open during blood draw fromthe vessel. The catheter body 500 is advanced along axis 504 in astraight configuration. In FIG. 3B, the catheter body 502 is shown in acoiled configuration allowing it to maintain the vessel 402 open duringblood draw, maintaining the vessel at diameter D1. The coiled catheterbody 502 can prevent the vessel 402 from collapsing to a degree thatwould substantially impede blood flow when blood is drawn by thecatheter 500. In certain implementations, where the catheter is advancedto a vessel upstream of the radial artery, e.g., the brachial, axillary,or subclavian artery, the respective artery may be held or propped openby the coiled catheter to avoid collapsing to a degree that wouldsubstantially impede blood flow or drawing blood.

In some implementations, e.g., where the catheter is configured to drawblood at the radial artery without advancement to the subclavian artery,the radial artery may be propped open such as by a sheath or by thecatheter body. For example, the catheter body may have a spiral orcoiled shape to prop open the radial vessel, in which blood flowsthrough a center or central portion or lumen of the catheter body. Insome implementations, the catheter comprises a straight lumen. In someimplementations, the catheter comprises a coiled lumen configured toprop open a vessel of the patient. In some implementations, the cathetercomprises a straight configuration upon insertion and assumes a coiledconfiguration inside the artery or vessel. In some implementations, thecatheter body is formed from a shape memory material (e.g., nickeltitanium, such as Nitinol). In this example, the catheter body may beinserted into the radial artery in a straight configuration. Onceinserted, the catheter is configured to coil and prop the radial arteryvessel open to prevent collapse during blood draw (e.g., as shown inFIGS. 3A-3B). In certain implementations, where the catheter is advancedto a vessel upstream of the radial artery, e.g., the brachial, axillary,or subclavian artery, the respective artery may be held or propped opento avoid collapsing to a degree that would substantially impede bloodflow or drawing blood.

Returning to FIG. 1 , the draw line 124 may include a bubble trapchamber 120 and is configured to interface with a pump 118 and may beconfigured to interface with a first flow control mechanism, e.g., adraw line flow control mechanism 122 of the delivery system 100.Pressure transducers 138 a-b may be located on either side of the pump118 to measure pressure of blood flowing through the blood circuit, suchas through the draw line 124, through the return line 130, or througheach of the draw line and the return line.

The delivery system may include a flow sensor 146, for example on ornear the blood circuit (e.g., on the draw line (not shown) or returnline 130) to measure the flow rate of the blood circulation in the bloodcircuit. For example, the flow sensor 146 can measure a number ofmilliliters per minute (mL/min) of blood drawn or gas-enriched blooddelivered to the patient 144. In some implementations, the flow sensor146 is positioned near the pump 118. In some implementations, the flowsensor is positioned near the return line 130 or near connectors 138 aor 138 b.

To deliver gas-enriched blood to a patient 144, the delivery system 100operates as follows. The delivery system 100 console 102 is connected toeach other component of the delivery system. For example, the cartridge200 is inserted into the cartridge housing 104 of the console 102.Tubing (e.g., the draw and return lines 124, 130) extending from thecartridge and connecting the cartridge 200 to the catheter 136 may beinterfaced with the draw flow control mechanism 122, and/or return flowcontrol mechanism 128, and pump 118 of the console. The cartridge anddraw and return lines 124, 130 may be configured such that uponinsertion of the cartridge into the cartridge housing, the tubingautomatically self-aligns with the draw flow control mechanism 122and/or return flow control mechanism 128, and/or pump. For example, thecartridge may have return and draw lines, which have a predefinedorientation and shape that match with a corresponding shape or design inthe cartridge housing and/or on the console. The predefined orientationand shape is such that upon insertion of the cartridge into thecartridge housing, the draw line and return line automatically alignwith and interface with the draw and/or return flow control mechanisms122, 128, and the pump 118. The power supply 114 is connected to anexternal power source for providing power to the console 102. The oxygensupply 110 receptacle is provided an oxygen bottle 112 for providing thesource of oxygen to the cartridge 200. The user interface 132 canindicate whether any of these consumables are missing from the deliverysystem 100 before or when delivery of the gas-enriched blood to thepatient is beginning. In certain implementations, the cartridge and drawand return lines may be aligned by the user

Once each of the components of the delivery system are connected,including one or more of the cartridge 200, pump 118, bubble trap 120,bubble detector 126, draw flow control mechanism 122, return flowcontrol mechanism 128, and catheter 136, the delivery system 100 isready for use. The blood circuit is shown with arrows representing thedirection of blood flow during operation of the delivery system 100,where blood is pulled from the catheter 136 through the draw line,through the cartridge and returned to the catheter via the return line.

Prior to operation, a priming process is run which causes the bloodcircuit to be filled or substantially filled to a threshold level withblood such that there is no room air and/or air bubbles in the bloodcircuit, which could travel to the patient 144. For example, the drawline 124 and return line 130 are filled with blood. For example, thebubble trap 120 and pump 118, and the tubing connecting the variouselements of the blood circuit, are filled with blood. The blood mixingchamber of the cartridge 200 is filled with blood, e.g., to a thresholdlevel.

Room air and/or air bubbles from each of the elements of the bloodcircuit is vented from the respective elements, as subsequentlydescribed. The bubble detector 126 is configured to detect any bubblespresent in the blood circuit during operation of the delivery system 100and can send a signal resulting in the closing of the return flowcontrol mechanism 128 if room air and/or air bubbles are detected in theblood circuit. This prevents air bubbles from reaching the patient 144at the catheter 136. The bubble detector 126 can include an ultrasonicsensor, infrared (IR) sensor (e.g., a photogate), or other suchmechanism for detecting air or bubbles in line. For example, the bubbledetector 126 can include an IR sensor that senses an IR beam sentthrough the fluid of the blood circuit. An air bubble in the fluiddistorts the beam, which can be detected by an IR sensor.

The delivery system 100 may be configured to control the oxygen levelsin the blood and/or tissues of the patient 144 by controlling the oxygenlevels in the supersaturated oxygen liquid or solution, (e.g., targetinga dissolved O₂ concentration in saline of 0.1 ml O2/ml liquid (STP) orgreater or 0.1-6 ml O₂/ml liquid (STP) or 0.2-3 ml O₂/ml liquid (STP)and/or the flow rate of the supersaturated oxygen enriched blooddelivered to the patient 144, e.g., by controlling the speed of the pumpto achieve a target blood flow rate of ml/min, 30-300 ml/min or 50-150ml/min. The system 100 may be configured to titrate oxygen into liquide.g., saline, to be mixed with blood and adjust the oxygen level and/orblood flow rate, until the desired oxygen level is achieved (e.g., asmeasured by a blood oxygen sensor in the patient 144). In an example,the concentration of oxygen delivered, and/or blood flow rate may bemodulated during treatment based on feedback from one or more sensorsmeasuring various patient and/or system parameters.

One example of a sensor for measuring a partial pressure (pO₂) of oxygenor oxygen saturation SO₂ in the patient's blood is a pulse oximeter. Apulse oximeter may be used for estimating arterial pO₂ or SO₂. Pulseoximetry estimates the percentage of oxygen bound to hemoglobin in theblood. A pulse oximeter uses light-emitting diodes and a light-sensitivesensor to measure the absorption of red and infrared light. In anotherexample, a sensor for measuring partial pressure of oxygen comprises anelectrode such as a Clark electrode for measuring pO₂. A Clark electrodeis an electrode that measures ambient oxygen concentration in a liquidusing a catalytic platinum surface according to the net reaction O₂+4e⁻+4 H+→2 H₂O. The various sensors may be coupled to a controller of thesystem via a cable or other wired connection or via a wirelessconnection.

As discussed herein, one or more blood pressure sensors may be used tomeasure blood pressure values in blood from a patient receivinggas-enrichment therapy. A processor of the controller receives signalsfrom the blood pressure sensor, which correspond to the measured valuesof blood pressure and changes in blood pressure. The processor maycompare the measured blood pressure to a target range of blood pressure,e.g., blood pressure in a healthy individual. The processor may generatean alert, e.g., through the user interface, that indicates the bloodpressure or a change in blood pressure. The measured blood pressure orchange in blood pressure may indicate the effectiveness of thesupersaturated oxygen or gas therapy, letting the caregiver know if theblood pressure is within a target range in order to optimize the SSO2therapy. The processor may control the gas enrichment system bymodifying one or more saline or blood parameters in the gas-enrichmentsystem to optimize therapy based on the blood pressure feedback.

A change in blood pressure may be indicative of a change in blood flowin myocardial tissue in response to the gas-enrichment therapy. Thegas-enrichment therapy, e.g., SSO2 therapy, provides a highconcentration gradient of O2 that enables increased diffusive transferto ischemic areas of myocardium. This diffusive transfer of O2 to areasmost in need does not depend on blood flow and thus O2 can easily accessthe endothelial cells of capillaries suffering from edema (swelling).SSO2 therapy is able to reverse this edema response in themicrovasculature and restore flow, nurturing surrounding heart tissuewith oxygenated blood.

In addition to the wire with pressure sensors discussed above, anotherexample sensor for measuring an arterial pressure of the patient's bloodincludes a pressure sensor positioned in or coupled to the catheter. Thecatheter may be connected to a fluid-filled system or pressure tube,which is connected to an electronic pressure transducer and/or pressuremonitor. A change in detected blood pressure may be indicative ofimproved perfusion and/or restored flow in ischemic tissue as a resultof the SSO2 therapy. The therapy may result in improved heart function.In certain implementations, the processor may control the delivery ofSSO2 therapy based on the arterial pressure feedback.

In certain implementations, feedback may be based on a measured bloodpressure waveform. A change in a waveform reflection pattern may bedetected. In one example, changes in the reflection pattern of thenormal pulsatile waveform of the patient's blood pressure may bedetected or measured. In another example, a pulsatile flow may becreated (for more fine tuning), and changes in the reflection patter ofthe created pulsatile waveform of the patient's blood pressure may bedetected or measured. In either example, the pulsatile waveform may beanalyzed for information, such as the relative magnitude and the timingof the secondary peak identified in that waveform.

The processor of a controller 102 can receive the signals from thesesensors, which signals correspond to the measured values of pO₂. Theprocessor compares the measured pO₂ to a target range of blood pO₂,e.g., 760-1500 mmHg. The target range can be calculated based on asource input blood pO₂ of 80 mmHg, a blood flow rate of 50-150 ml/min,an SSO₂ saline flow rate of 2-5 ml/min and dissolved O₂ concentration insaline of 0.2-3 ml O₂/ml saline (STP). The controller can adjust any ofthe above parameters based on the measured pO₂ in blood to achieve anarterial blood pO₂ within the target range. The processor may generatean alert, e.g., through a user interface, audible alarm and/or visualalarm that indicates the level of pO₂. The measured pO₂ indicates theeffectiveness of the supersaturated oxygen therapy, letting thecaregiver know if the pO₂ in blood is within the target range foroptimizing the delivery of oxygen to the patient's ischemic tissue. Incertain implementations, the processor may control the delivery ofsupersaturated oxygen therapy by modifying one or more of the abovereferenced saline or oxygen parameters based on the signals receivedfrom the sensors.

Another example of a sensor is an O₂ fluorescence probe. Thefluorescence probe may be coupled to a controller of the system via acable or other wired or wireless connection. A light source of the O₂fluorescence probe is illuminated. A fiber optic cable can be used toprovide light to the light source in certain implementations, where thefiber optic cable is connected to the controller of the system. Thefluorescence of a sensor molecule of the O₂ fluorescence probe ismeasured. The sensor molecule can include fluorophore. A signal isreceived by the processor from the O₂ fluorescence probe based on thefluorescence measurement. Fluorescence is measured by measuring thelifetime or decay of the fluorescence intensity signal from theilluminated sensor molecule (e.g., fluorophore) on the fluorescenceprobe. The decay of this signal is caused by the quenching effect ofoxygen molecules in the blood or in tissue on the fluorescence intensitysignal of the sensor molecule. The processor can determine the oxygenconcentration, SO₂ or pO₂ in blood or tissue based on the quenchingeffect of oxygen on the florescence intensity signal of the florescenceprobe. Changes in a time that is required for the signal to decay due tooxygen quenching are indicative of the local oxygen concentration, SO₂or pO₂ in blood or tissue. The processor generates an alert, e.g.,through a user interface, audible alarm and/or visual alarm, based onthe determined oxygen concentration, SO₂ or pO₂ in blood or tissue. Thealert may indicate the effectiveness of the supersaturated oxygentherapy. The determined oxygen concentration, SO₂ or pO₂ indicates theeffectiveness of the supersaturated oxygen therapy, letting thecaregiver know if the oxygen concentration, SO₂ or pO₂ in blood iswithin a predefined target range (e.g., the expected range for a healthyindividual) for optimizing the delivery of oxygen to the patient 144. Incertain implementations, the processor may control the delivery ofsupersaturated oxygen therapy by modifying one or more of the saline oroxygen parameters, e.g., saline flow rate or dissolved O₂ concentrationin saline, based on the determined oxygen concentration, SO₂ or pO₂values.

The user interface 132 is configured to display operational data and/orpatient data on the user interface in a configuration that allows a userto determine a status for the SSO₂ liquid and gas-enriched blooddelivery to the patient 144. The user interface 106 shows a currentoperational status of the delivery system 100.

These values can be stored as a time sequence of data entries or logentries in an operational log. The user interface may include a visualrepresentation of the operational log, the visual representationincluding operational data specifying how the delivery system 100 isperforming during delivery of the enriched blood to the patient. Forexample, the delivery system 100 logs sensor readings during deliveryand generates an alert or report indicating whether the delivery of thegas-enriched blood should be titrated. In some implementations, thedelivery system 100 can send logged data to remote, networked storage(e.g., in cloud storage) for access from one or more networked devices.

In some implementations, various data elements are logged during thedelivery process. For example, the duration of delivery can be logged.Each time a checkpoint is reached, a time stamp associated with thecheckpoint is saved. Checkpoints can include completion of the deliveryprocess, indication of titration of the delivery of gas-enriched blood,indication of values of one or more physiological parameters such aspressure or flow rate, a visualization of an estimate of themicrovascular resistance, or any other data of interest during thedelivery process. The values of sensors, such as the level sensors,pressure sensors and temperature sensors, can be stored at giveninstances in time. The operational values of devices on the bloodcircuit can be monitored, such as how fast the pump is operating, bloodlevels in the blood mixing chamber or bubble trap, when one or more flowcontrol mechanisms 122, 128 are actuated, and so forth. These dataprovides information to determine whether an issue is occurring duringdelivery of the gas-enriched blood.

In some implementations, the delivery system 100 may include aprocessor, a memory, and associated circuitry coupled to the one or moresensors for detecting physiological data. The physiological data iscollected and/or stored in the system for retrospective, current orother review. The delivery system 100 is configured to generate logentries for the operational data (e.g., delivery data). The log entriesmay be displayed on the user interface 132. In certain implementations,the log entries can each be structured messages that include particularvalues associated with the operation of the delivery system 100,generated from data messages. In some implementations, a data message(also called a log message) represents an instant snapshot of theoperational data. For example, a data message can include treatment dataor current pO₂ and SO₂ values at a given time (e.g., associated with atime stamp). In some implementations, a data message can include datarepresenting a treatment period or system mode of the gas-enrichedliquid treatment for the patient 144 in a structured log entry. The datamessages are stored in a digital format that enables streaming of thedata messages to a remote system. The remote system is configured toquickly extract the values representing the patient data and theoperational data of the delivery system 100 and display a representationof these data on a local or remote user interface. For example, datamessages can be formatted for streaming to an operator or nurse'sstation from a hospital room. In some implementations, data messages caninclude warnings or alerts that prompt intervention from a user of theremote system. In some implementations, the data messages can be storedin a structured format that facilitates searching and retrieving ofoperational data for the patient 144 for operation of the deliverysystem 100 during SSO₂ delivery.

In some implementations, the log entries can each be structured messagesthat include particular values associated with the operation of thedelivery system 100, generated from data messages. For example, the datamessages can indicate a current snapshot of the operation of thedelivery system 100. In this case, the values of the data messageinclude a list of operational values and/or physiological values. Theoperational values and/or physiological values can be parsed from thedata messages (e.g., by a remote device) and used to populate a screenor display of a remote computing system. For example, the deliverysystem 100 can transmit a stream of data including the data messages toa remote system for remote monitoring of the operation of the deliverysystem 100. In some implementations, the processor is configured tostream digital output data having the patient data and the operationaldata to a remote server. In some implementations, operational andpatient data may be transmitted or streamed in real time or near realtime via a wired, RS-232 streaming output on the system console to aremote processor or computer, e.g., to an EMR data hub or hospital hub.In some implementations, operational and patient data may be transmittedor streamed in real time or near real time over a WiFi communications,Bluetooth, cellular, USB or other wireless connection or link.

The data messages can include summary data. For example, log entries caninclude data representing a summary of operational and/or physiologicaldata for a time period (e.g., pre-titration data, titration data, andpost titration data). Each log entry may form all or a portion of theoperational log, which provides an overall summary of the operation ofthe delivery system 100. The operational log allows a medical serviceprovider to quickly review the summary of the operation of the deliverysystem 100. The operational and/or physiological data, e.g., datamessages, log entries, operational log and/or other data, stored by thesystem processor or an accessary to the system or data module, coupledto the system console, may be stored on volatile or non-volatile memory.The log entries can be visually represented on the user interface 132.

Data messages may provide instant values of operational data of thedelivery system 100 and the physiological data. Log entries mayrepresent data gathered over time and can be part of a system and/orpatient profile. For example, the operational log and the log entriescan be stored in electronic medical records (EMR).

In some implementations, the log entries of the operational log aretransmitted to a remote device (such as a data hub in a hospital). Thedelivery system 100 sends the data including the log entries to theremote device in one or more different ways. The delivery system 100sends the log entries data to a remote device in response to a trigger.For example, the delivery system 100 can send the log entries to theremote device once titration of delivery of the gas-enriched blood iscompleted. In some implementations, the delivery system 100 sends theoperational log data once all treatment is completed. For example, whenthe cartridge 200 is removed or the pump 118 is powered off, thecontroller 102 can determine that treatment is completed and send thelog entry data to the remote device.

In some implementations, the delivery system 100 sends the operationallog data to the remote device upon detecting a fault, such as a bubbletrap 120 fault, a catheter 136 fault, a patient SO₂ or pO₂, or bloodpressure or flow rate value failing a threshold, etc. The operationallog data can be analyzed (e.g., by a user) to determine why the faultoccurred and/or to determine whether operation of the delivery system100 is adversely impacted by the fault. This enables the user to takecorrective measures immediately (e.g., replacing a bubble trap 120,fixing a fluid leak, etc.) to ensure that treatment of the patient 144is not compromised.

In some implementations, the delivery system 100 sends the operationallog data without a trigger. For example, the delivery system 100 cansend the log entry data to the remote device periodically (e.g., onceper minute, once per hour, and so forth).

In an aspect, the delivery system 100 links the log entries related tooperation together in a structured format. For example, a key value canbe stored with each log entry. The entire log of the operation of thedelivery system 100 can be retrieved by referencing the key value.

The delivery system 100 can generate one or more alerts to indicate astatus of one or more components of the delivery system 100. The alertscan be generated based on the operational log data or data of the datamessages. The alert can be generated for presentation on a userinterface 132 of the delivery system 100. The processor may send thealert to one or more other computing devices, such as computing devicesassociated with a health care provider of the patient 144. In an aspect,a user interface is configured to communicate with the processor,wherein the data representing the alert indicating whether a fault hasoccurred, priming has initiated/completed, or any other relevant aspectof the operation of the delivery system 100 that satisfies anotification rule causes a notification to be displayed on a userinterface. The user interface may be coupled to the console via a wireor wirelessly (e.g., the user interface may be a portable tablet orremote computing device)

The alert may indicate that there is a fault or error in operation ofthe delivery system 100. The alert provides an indicator for a healthcare provider to investigate the operation of the delivery system 100,such as to investigate whether any faults have occurred. The alerts mayindicate that titration of the delivery of the gas-enriched blood hascompleted, that there is a pressure over value in the blood circuit,that room air and/or air bubbles have been detected, etc.

In some implementations, the processor generates the alert to cause oneor more devices to perform an action. For example, feedback can bepresented to a healthcare provider, such as an audio cue, visualpresentation, and so forth. The alert can cause a device to contact ahealthcare provider (e.g., place a phone call or page to a physician,nurse, etc.). The alert can cause a device to display particular dataabout the delivery process or performance of the system, or data aboutthe patient 144, such as a presentation of the patient's SO₂ and/or pO₂or blood pressure or flow rate values over a given treatment period. Thealert can cause a device to update a health record associated with thepatient 144 or cause the device to retrieve a health record associatedwith the patient for further analysis. In certain implementations, theprocessor of the system may be configured to determine if the alert is areal time alert or recorded for retrospective review. If it is a realtime, the processor determines whether to display the alert on the userinterface, transmit the alert in an information chain, or send the alertdata to a third-party monitor. An example route is to send the alert toa physician or nurse's cell phone.

The alert may open a cell phone-based application or open anInternet-based application. From either application the physician ornurse could see the alert plus other relevant data that may have beentransmitted. The alert may include a hospital specific patientidentifier, but otherwise be invisible as to the identity of the patient144, unless the physician or the hospital has added the patient's nameto either the application on their phone or to the Internet. The alertmay include a non-patient specific identifier such as a bed number.Additionally, the physician would have the opportunity to take actionsin response to receiving the alert. This might include triggering aphone call to the ICU desk or marking that the physician has seen thealert. Changing the duration or range of a monitored value would allowthe user to set a duration so that a transient spike would not triggerthe alert. In the case of adjusting the time and/or duration of thealert, such an adjustment may only affect the notification to thatspecific person.

A dual alert to a nurse or physician might have different alert rangesand actions. The described features may put the user, e.g., physician incomplete control. For example, the first point of control may be at thebedside, where the alert ranges may be set. The second point of controlmay be at the receiving application or website where the user may adjustnominal settings, e.g., for “tones”. As such, two or more triggers maybe established: the first is to “send” the alert from the machine intothe network to the receiving device; and the second is the action thatthe receiving device takes upon receiving the alert. A schedulingfeature may also be provided that allows for the transfer data from onephysician going off shift to another coming on shift. A response treemay be provided that requires an acknowledgement that the alert has beenseen or transferred from one physician to another. For example, a firstdoctor is given 5 minutes to acknowledge receipt of the alert, and if noacknowledgment is made, the alert is sent to another physician or nurse.In certain implementations, one or more of the various alerts or alertparameters described herein may be customized by the user. Multipleoptions for alert delivery, e.g., device display, nurse's station, EMR,cell phone, etc. may be set. An alert for thermoregulatory activity of apatient 144 may include other forms. For example, a color scale oraudible alert may be output via the user interface to provide a valueindicative of patient activity.

In some implementations, a medical service provider can query thedelivery system 100 to obtain the operational data. The query canrequest particular data, such as what the battery status is, determinewhether titration of gas-enriched blood was successful, and so forth.

In some implementations, a controller is configured to store digitaloutput data representing the delivery process in a data store. Thecontroller is configured to detect that a trigger condition of thedelivery process is satisfied. For example, the trigger condition caninclude completion of all or a portion of the delivery process. In someimplementations, the controller, in response to detecting that thetrigger condition is satisfied, transmits the digital output data to aremote device in real time or in near real time, e.g., during or afterthe delivery of gas-enriched blood by the delivery system.

In some implementations, the digital output data includes a predefinedformat that enables the digital output data to be streamed to a remotedevice. The delivery system can include a transmitter configured totransmit the digital output data to the remote device. In someimplementations, the predefined format is configured to enable theremote device to parse the digital output data for displaying theoperational SO₂ or pO₂ or blood pressure or flow rate data and/or theoperational data upon receiving the digital output data. In someimplementations, the process includes streaming the digital output dataover a WiFi communications, Bluetooth, cellular, or other wirelessconnection or link or USB. In some implementations, the process includestransmitting the digital output data over a wired connection.

FIG. 4 is a diagram of an example of a portion of the system of FIG. 1including the cartridge 200. In this example, the cartridge 200 includesa fluid supply chamber (piston device 202), a gas enrichment chamber (anoxygenator 204), and a blood mixing chamber 206. In someimplementations, the cartridge 200 may also include a bubble trap 208,and at least a portion of the draw line 214 tubing and the return line218 tubing. In FIG. 4 , the pump 210 is similar to pump 118, the drawline 214 is similar to draw line 124, the return line 218 is similar toreturn line 130, and the bubble trap 208 is similar to bubble trap 120.The cartridge 200 is consumable portion of the blood circuit thatincludes portions of the blood circuit that contact the patient's blood.The return draw flow control mechanism 216, pump 210, and draw flowcontrol mechanism 212 are shown in dashed lines because these are a partof the console system and are reusable. Similarly, the return pressuresensor 238 and/or the draw pressure sensor 240 are reusable; however, incertain embodiments, the return pressure sensor 238 and/or the drawpressure sensor 240 may be part of the single use consumable cartridgeand tubing. In some implementations, the return pressure sensor 238 thedraw pressure sensor 240, the bubble trap 208, and/or the draw line flowcontrol mechanism 212 are optionally included in the delivery system 100or in the blood flow circuit.

The cartridge 200 is configured to interface with components of theconsole 102 of the delivery system 100 during operation, priming andtreatment. A portion of the tubing of the cartridge 200, which can becalled a pump tube, is configured to be placed in the pump 210 of theconsole. The draw line 214 tubing and the return line 218 tubing areoriented to be placed inside the draw flow control mechanism 212 and thereturn flow control mechanism 216, respectively. The flow controlmechanisms 212, 216 are coupled to the console 102. When the cartridge200 is installed, the flow control mechanisms 212, 216 align with thedraw and return lines 214, 218 to enable the flow control mechanisms torestrict fluid flow (e.g., by clamping) in the draw and return lines214, 218. The draw flow control mechanism 212 and the return flowcontrol mechanism 216 are actuated by control signals of a controller ofthe console 102. Similarly, the pump 210 is coupled to the console 102.The pump 210 is activated by control signals of the controller of theconsole for pumping in either the draw line direction or the return linedirection as needed.

The piston device 202 includes a mechanical device for drawing salinefrom the fluid source. The fluid from the IV source is drawn throughtubing into a piston chamber. The piston moves vertically in the chamberbased on signals from a piston actuator. A load cell determines theforce required to move the piston. A stepper motor controls the motionof the actuator. An encoder reports the piston position based on thestepper motor rotor location. A piston top sensor and piston bottomsensor can detect when the piston moves to an edge of the chamber. Theposition of the piston determines how much fluid from the saline bag issent to the oxygenator.

The piston device 202 is configured to draw saline into the oxygenator204. The oxygenator 204 is configured to add oxygen to the saline fromthe saline bag 106. An oxygen pressure line 220 adds oxygen to theoxygenator 204. The oxygenator 204 is coupled to an oxygen vent 226 andan oxygen vent solenoid 228 that controls operation of the vent 226. Theoxygenator vent 226 is configured to vent excess air from the oxygenatorif the oxygen pressure exceeds a threshold value.

The oxygenator 204 includes an oxygen chamber, an atomizer, and a valvemanifold. The valve manifold includes several valves such as a fillvalve, a flush valve, and a supersaturated oxygen SSO₂ flow valve (notshown). Each of the fill valve, flush valve, and SSO₂ flow valve arecontrolled by a respective solenoid. A fill solenoid opens/closes thefill valve. A flush solenoid opens/closes the flush valve. A SSO₂ flowsolenoid opens/closes the flow valve. An SSO₂ level sensor 400 indicatesa level of the gas-enriched liquid in the oxygenator.

The oxygen chamber is connected to the oxygen pressure line and theoxygen vent. The oxygenator releases excess oxygen through oxygen vent426 and receives additional oxygen through oxygen pressure line. Theoxygenator receives fluid from the piston chamber. The atomizer includesa central passageway in which a one-way valve is disposed. When thefluid pressure overcomes the force of the spring in the one-way valveand overcomes the pressure of the oxygen within the atomizer chamber,the fluid travels through the passageway and is expelled from a nozzleat the end of the atomizer.

The nozzle forms fluid droplets into which the oxygen within theatomization chamber diffuses as the droplets travel within theatomization chamber. This oxygen-enriched fluid is referred to a SSO₂solution. The nozzle is preferably a simplex-type, swirled pressurizedatomizer nozzle including a fluid orifice of about 0.004 inches diameterto 0.005 inches diameter. The droplets infused with the oxygen fall intoa pool at the bottom of the atomizer chamber. Since the atomizer willnot atomize properly if the level of the pool rises above the level ofthe nozzle, the level of the pool is controlled to ensure that theatomizer continues to function properly. Once the oxygen has beendissolved into the saline using the controlled pressure, thegas-enriched saline is sent to the blood mixing chamber 206 for mixingwith blood in the blood circuit.

The blood mixing chamber 206 is connected to the oxygenator 204. Theblood mixing chamber 206 is thus a part of the blood circuit. The bloodmixing chamber 206 is positioned between the pump 210 tubing and thereturn line flow control mechanism 216 and bubble detector 126. A bloodmixing chamber vent 230 is configured to vent any room air and/or airbubbles from the blood mixing chamber 206. A blood mixing chamber ventsolenoid 232 controls operation of the vent 230.

The blood mixing chamber 206 includes a volume configured to receivegas-enriched saline from the oxygenator 204. The blood mixing chamberincludes low sensor and a high sensor. The low sensor is configured todetect when the blood mixing volume 502 is empty. The high sensordetects when the blood mixing volume is full.

The blood mixing volume vents room air and/or air bubbles from the bloodcircuit through the vent through the line. The blood mixing chamberreceives gas-enriched saline from the oxygenator. The blood mixingchamber receives blood from the pump 210 from the pump tube duringoperation of the delivery system 100. The gas-enriched saline from theoxygenator 204 mixes with the blood from the draw line of the bloodcircuit. A return pressure sensor measures pressure in the blood circuiton the return line side of the pump 210. The blood from the bloodcircuit passes through the blood mixing volume and mixes with thegas-enriched saline from the oxygenator 204. The return line draws bloodout of the blood mixing volume to the bubble detector 126.

The blood mixing chamber 206 oxygenator and piston chamber may belocated in a single housing or separate from one another. The pump 210is configured to interface with a pump tube. The pump tube connects thebubble trap 208 to the pump 210. The pump tube connects the blood mixingchamber 210 to the pump on of the opposite side of the pump 210 from thebubble trap 208. Blood in the blood circuit during operation of thedelivery system 100 thus comes from the draw line 214 through the bubbletrap, is pumped by the pump 210, goes through the blood mixing chamber206, and then goes through or passes by the bubble detector 126 in thereturn line 218.

A bubble trap 208 may be provided and configured to remove room airand/or air bubbles from the blood circuit. The bubble trap 208 has abubble trap volume configured to receive blood from the draw line. Thebubble trap volume vents room air and/or air bubbles from the volume tothe bubble trap vent. Bubbles rise to the top of the volume and arevented. The bubble trap volume has a low sensor to detect when thebubble trap volume is empty. The bubble trap volume has a high sensor todetect when the bubble trap volume is full. When the volume is full ofblood, the bubble trap 208 is primed. Venting of the bubble trap 208through a bubble trap vent 234 can be controlled by a bubble trapsolenoid 236, which is actuated for venting the bubble trap.

FIG. 5 shows the system 100 of FIG. 1 for administering SSO₂gas-enrichment therapy, e.g., SSO₂ therapy in greater detail. The system100 for administering SSO₂ therapy generally includes three componentdevices: the main control system, the gas enrichment system (e.g.,oxygenation cartridge), and the infusion device (e.g., an infusioncatheter). These devices function together to create a highlyoxygen-enriched saline solution called SSO₂ solution. Blood is mixedwith the SSO₂ solution producing supersaturated oxygen enriched blood.The supersaturated oxygen enriched blood is delivered to the patient.The system 100 may have a modular design comprising three removablemodules such as a base module 340, the mid-section control module 342,and the display module 346. The system 100 may also have a sensingcatheter 338, which can be implemented via a catheter (e.g., catheter136) in accordance with certain implementations, or may have othersensing or imaging inputs. A gas tank receptacle 346 is provided on thebackside of the base module 340 for receiving and housing a standard“B-bottle” USP oxygen tank 348. The oxygen tank 348 is mounted to thesystem via a gas tank adapter. A suitable gas, such as oxygen, isdelivered from the oxygen tank 348, to a second chamber within anoxygenation cartridge. The physiologic liquid, e.g., saline, from afirst chamber is pumped into the second chamber and atomized to create asupersaturated oxygen enriched physiologic solution. This supersaturatedoxygen enriched physiologic solution is then delivered into a thirdchamber of the oxygenation cartridge along with the blood from thepatient. As the patient's blood mixes with the supersaturated oxygenenriched physiologic solution, supersaturated oxygen enriched blood iscreated and then delivered to a targeted major epicardial artery, e.g.,the left main coronary artery, via an infusion catheter.

Each of the three modules 340, 342, 344 of the system 100 may includedoors or access panels for protecting and accessing the variouscomponents housed therein. For example, the mid-section control module342 includes a hinged door 336 for enclosing the gas-enrichment system(i.e. the cartridge) and access panel 350 for covering the access windowto the internal space of the module. A safety switch (e.g. an emergencystop switch 352) may be provided so that a user can initiate a shutdownof the system in the same fashion even if the system is operating withinits prescribed bounds.

In the above particular embodiment, the body of the base module 340 ismade up of a tubular chassis situated on a circular-shaped pedestal 354.A plurality of wheels are mounted on the bottom of the circular-shapedpedestal to provide mobility for the system. The wheels have a lockingmechanism for keeping the wheels stationary. The base chassis housescertain electrical and mechanical components including a battery (notshown), a power supply (not shown), and connectors for connecting thebase module 340 to the mid-section main module 342. The user interface134 includes a screen 330, buttons 332, knobs 334, and other controlsfor interaction with the delivery system 100.

FIG. 6 shows a flow diagram of a process 600 for gas-enrichment, e.g.,SSO₂, therapy delivery by one or more of the systems described herein,such as in relation to FIG. 1A-FIG. 5 . The process 600 for deliveringgas-enriched blood within a vasculature of a patient includes providing(602) a gas-enrichment system, the gas-enrichment system comprising amixing chamber and a blood pump. The process 600 includes inserting(604) a catheter for drawing blood from the patient into a radial arteryof the patient. The process 600 includes advancing (606) the catheterdistal end to a vessel upstream of the radial artery. The process 600includes drawing (608) blood from the vessel upstream of the radialartery at a blood flow rate without collapsing the vessel to a degreethat would substantially impede blood flow or drawing blood. The process600 includes generating (610) a gas-enriched blood by mixing thewithdrawn blood with a gas-enriched liquid in the mixing chamber. Theprocess 600 includes delivering (612) the gas-enriched blood to thevasculature of the patient.

In some implementations, the catheter is advanced to a vessel upstreamof the radial artery and the blood is drawn from the vessel upstream ofthe radial artery. For example, the catheter is advanced to thesubclavian artery. In some implementations, the blood flow rate is ablood flow rate or predetermined blood flow rate of 10-500 ml/min,30-300, or 50-150. In some implementations, an inner diameter and lengthof the catheter are sufficient to support a blood flow rate orpredetermined blood flow rate of 50-150 ml/min while avoiding a pressuredrop that would cause pump cavitation. In some implementations, theouter diameter is 6-7 French, the length is 10-100 cm, and the pressuredrop is from 0 mmHG to negative 100) mmHG.

In some implementations, inserting the catheter into a radial artery ofthe patient includes, for process 600, accessing a brachial, axillary orsubclavian artery of the patient through the radial artery. In someimplementations, the process 600 includes advancing the catheter intothe brachial, axillary or subclavian artery for drawing the blood fromone or more of said arteries.

In some implementations, inserting, for the process 600, the catheterinto the vasculature of the patient includes inserting a sheath into thevasculature of the patient, the sheath configured to support thecatheter in the vasculature of the patient. In some implementations, theprocess 600 includes inserting the catheter into the sheath.

In some implementations, the sheath comprises a braided wire and aplastic liner over the braided wire. In some implementations, the sheathis between 50-100 centimeters in length. In some implementations,inserting the catheter into a radial artery of the patient, for process600, includes advancing the catheter into the radial artery or a vesselupstream of the radial artery of the patient until distal band on thecatheter aligns with a predetermined location in the vasculature of thepatient.

In some implementations, the process 600 includes controlling a drawrate of the catheter. Controlling the draw rate in process 600 includesdetermining a maximum draw rate based on a size of the radial artery orvessel upstream from the radial artery. Controlling the draw rate inprocess 600 includes determining a minimum draw rate and a draw pressurebased on a pump flow requirement of a pump configured to draw the bloodfrom the radial artery or a vessel upstream of the radial artery.Controlling the draw rate in process 600 includes controlling the drawrate to be between the maximum draw rate and the minimum draw rate. Insome implementations, the maximum draw rate is a draw rate above whichwould cause a collapse of the radial artery or a vessel upstream of theradial artery to a degree that would substantially impede blood flow ordrawing blood. In some implementations, the draw rate is a function of alength of the catheter for process 600. In some implementations, thecatheter can be configured for a minimum draw rate of 100 milliliters(mL) per minute and wherein the draw pressure is at least 50 millimetersper Mercury (mmHg).

The process 600 may include measuring the draw rate using a flow sensor.The process 600 may include generating an alert in response tomeasuring, by the flow sensor, that the draw rate is greater than themaximum draw rate or is less than the minimum draw rate.

The process 600 may include measuring the draw pressure using a pressuresensor. The process 600 may include generating an alert in response tomeasuring, by the pressure sensor, that the draw pressure is greaterthan a maximum draw pressure. In some implementations, one or morelumens of the catheter comprise a braided pattern. In someimplementations, the braided pattern comprises a rectangular crosssection. In some implementations, one or more lumens of the cathetereach comprise a wall thickness between 0.005 inches-0.015 inches, thewall thickness preventing kinking of the one or more lumens of thecatheter. In some implementations, one or more lumens of the cathetercomprise an atraumatic tip. In some implementations, the gas-enrichedblood is formed in the mixing chamber by mixing the blood withdrawn fromthe patient with the gas-enriched liquid generated by a gas enrichmentchamber. In some implementations, the gas-enriched liquid comprises asupersaturated oxygen liquid. In some implementations, thesupersaturated oxygen liquid has an O₂ concentration of 0.1-6 ml O₂/mlliquid (STP). In some implementations, the gas-enriched blood comprisesa supersaturated oxygen enriched blood. In some implementations, thesupersaturated oxygen enriched blood comprises a supersaturated oxygenenriched blood having a pO₂ of 600-1500 mmHg.

The process 600 may include inserting a second catheter into a secondradial artery of the patient for delivering the gas-enriched blood tothe vasculature of the patient.

In some implementations, a control signal corresponding to a measuredvalue of one or more physiological parameters may be received and usedto control a pump configured to draw blood from the patient and pump thegas-enriched blood for delivery into the patient. A process may includecausing the pump to pump blood to and from the gas-enrichment system andthe patient based on sending the control signal to the pump. The sensorcan include a flow sensor. The one or more physiological parameters mayinclude a flow rate of blood in the vasculature of the patient. In someimplementations, the sensors may include a pressure sensor. The one ormore physiological parameters may include a pressure of blood in thevasculature of the patient. In some implementations, the processincludes sending, by the controller, the control signal to a pumpconfigured to draw blood from the patient and pump the gas-enrichedblood for delivery into the patient. The process includes causing, basedon sending the control signal or an alert, the pump to increase a pumpspeed or reduce a pump speed to increase or reduce the amount or rate ofblood drawn from the patient and the amount or rate of gas-enrichedblood delivered to the patient. In some implementations, generating thecontrol signal or an alert is performed in real-time or near-real timeduring delivery of the gas-enriched blood to the patient. The deliveryof the gas-enriched blood to the patient is not paused duringmeasurement of the one or more physiological parameters. The measurementof the one or more physiological parameters represents a contemporaneousstatus of the patient for the delivery of the gas-enriched blood to thepatient.

In some implementations, receiving one or more signals corresponding toa measured value of the one or more physiological parameters from thesensor includes receiving a series of measured values of the one or morephysiological parameters from the sensor. The series of measured valuescan correspond to a period of time during delivery of the gas-enrichedblood to the patient. The process includes determining, based on theseries of measured values corresponding to the period of time, whetherthe value of the one or more physiological parameters is increasing ordecreasing over time. The process includes generating, based ondetermining that the value of the one or more physiological parametersis increasing or decreasing over time, the control signal or alert forincreasing or reducing the pump speed or rate or amount of blood drawnor gas-enriched blood delivered to the patient. The entire disclosuresof U.S. Pat. No. 6,743,196, U.S. Pat. No. 6,582,387, U.S. Pat. No.7,820,102 and U.S. Pat. No. 8,246,564 are expressly incorporated hereinby reference.

Some implementations of subject matter and operations described in thisspecification (e.g., process 600) can be implemented in digitalelectronic circuitry, or in computer software, firmware, or hardware,including the structures disclosed in this specification and theirstructural equivalents, or in combinations of one or more of them. Forexample, in some implementations, the processor of the delivery system(e.g., delivery system 100) can be implemented using digital electroniccircuitry, or in computer software, firmware, or hardware, or incombinations of one or more of them.

Some implementations described in this specification (e.g., theprocessor of the delivery system, etc.) can be implemented as one ormore groups or modules of digital electronic circuitry, computersoftware, firmware, or hardware, or in combinations of one or more ofthem. Although different modules can be used, each module need not bedistinct, and multiple modules can be implemented on the same digitalelectronic circuitry, computer software, firmware, or hardware, orcombination thereof.

Some implementations described in this specification can be implementedas one or more computer programs, i.e., one or more modules of computerprogram instructions, encoded on computer storage medium for executionby, or to control the operation of, data processing apparatus. Acomputer storage medium can be, or can be included in, acomputer-readable storage device, a computer-readable storage substrate,a random or serial access memory array or device, or a combination ofone or more of them. Moreover, while a computer storage medium is not apropagated signal, a computer storage medium can be a source ordestination of computer program instructions encoded in an artificiallygenerated propagated signal. The computer storage medium can also be, orbe included in, one or more separate physical components or media (e.g.,multiple CDs, disks, or other storage devices).

The term “data processing apparatus” encompasses all kinds of apparatus,devices, and machines for processing data, including by way of example aprogrammable processor, a computer, a system on a chip, or multipleones, or combinations, of the foregoing. The apparatus can includespecial purpose logic circuitry, e.g., an FPGA (field programmable gatearray) or an ASIC (application specific integrated circuit). Theapparatus can also include, in addition to hardware, code that createsan execution environment for the computer program in question, e.g.,code that constitutes processor firmware, a protocol stack, a databasemanagement system, an operating system, a cross-platform runtimeenvironment, a virtual machine, or a combination of one or more of them.The apparatus and execution environment can realize various differentcomputing model infrastructures, such as web services, distributedcomputing, and grid computing infrastructures.

A computer program (also known as a program, software, softwareapplication, script, or code) can be written in any form of programminglanguage, including compiled or interpreted languages, declarative orprocedural languages. A computer program may, but need not, correspondto a file in a file system. A program can be stored in a portion of afile that holds other programs or data (e.g., one or more scripts storedin a markup language document), in a single file dedicated to theprogram in question, or in multiple coordinated files (e.g., files thatstore one or more modules, sub programs, or portions of code). Acomputer program can be deployed for execution on one computer or onmultiple computers that are located at one site or distributed acrossmultiple sites and interconnected by a communication network.

Some of the processes and logic flows described in this specificationcan be performed by one or more programmable processors executing one ormore computer programs to perform actions by operating on input data andgenerating output. The processes and logic flows can also be performedby, and apparatus can be implemented as, special purpose logiccircuitry, e.g., an FPGA (field programmable gate array) or an ASIC(application specific integrated circuit).

Processors suitable for the execution of a computer program include, byway of example, both general and special purpose microprocessors, andprocessors of any kind of digital computer. Generally, a processor willreceive instructions and data from a read only memory or a random-accessmemory or both. A computer includes a processor for performing actionsin accordance with instructions and one or more memory devices forstoring instructions and data. A computer may also include, or beoperatively coupled to receive data from or transfer data to, or both,one or more mass storage devices for storing data, e.g., magnetic,magneto optical disks, or optical disks. However, a computer need nothave such devices. Devices suitable for storing computer programinstructions and data include all forms of non-volatile memory, mediaand memory devices, including by way of example semiconductor memorydevices (e.g., EPROM, EEPROM, flash memory devices, and others),magnetic disks (e.g., internal hard disks, removable disks, and others),magneto optical disks, and CD-ROM and DVD-ROM disks. The processor andthe memory can be supplemented by, or incorporated in, special purposelogic circuitry.

To provide for interaction with a user, operations can be implemented ona computer having a display device (e.g., a monitor, or another type ofdisplay device) for displaying information to the user and a keyboardand a pointing device (e.g., a mouse, a trackball, a tablet, a touchsensitive screen, or another type of pointing device) by which the usercan provide input to the computer. Other kinds of devices can be used toprovide for interaction with a user as well; for example, feedbackprovided to the user can be any form of sensory feedback, e.g., visualfeedback, auditory feedback, or tactile feedback; and input from theuser can be received in any form, including acoustic, speech, or tactileinput. In addition, a computer can interact with a user by sendingdocuments to and receiving documents from a device that is used by theuser; for example, by sending web pages to a web browser on a user'sclient device in response to requests received from the web browser.

A computer system may include a single computing device, or multiplecomputers that operate in proximity or generally remote from each otherand typically interact through a communication network. Examples ofcommunication networks include a local area network (“LAN”) and a widearea network (“WAN”), an inter-network (e.g., the Internet), a networkcomprising a satellite link, and peer-to-peer networks (e.g., ad hocpeer-to-peer networks). A relationship of client and server may arise byvirtue of computer programs running on the respective computers andhaving a client-server relationship to each other.

FIG. 7 shows an example computer system 900 that includes a processor910, a memory 920, a storage device 930 and an input/output device 940.Each of the components 910, 920, 930 and 940 can be interconnected, forexample, by a system bus 950. The processor 910 is capable of processinginstructions for execution within the system 900. In someimplementations, the processor 910 is a single-threaded processor, amulti-threaded processor, or another type of processor. The processor910 is capable of processing instructions stored in the memory 920 or onthe storage device 930. The memory 920 and the storage device 930 canstore information within the system 900.

The input/output device 940 provides input/output operations for thesystem 900. In some implementations, the input/output device 940 caninclude one or more of a network interface device, e.g., an Ethernetcard, a serial communication device, e.g., an RS-232 port, and/or awireless interface device, e.g., an 802.11 card, a 3G wireless modem, a4G wireless modem, a 5G wireless modem, etc. In some implementations,the input/output device can include driver devices configured to receiveinput data and send output data to other input/output devices, e.g.,keyboard, printer and display devices 960. In some implementations,mobile computing devices, mobile communication devices, and otherdevices can be used.

While this specification contains many details, these should not beconstrued as limitations on the scope of what may be claimed, but ratheras descriptions of features specific to particular examples. Certainfeatures that are described in this specification in the context ofseparate implementations can also be combined. Conversely, variousfeatures that are described in the context of a single implementationcan also be implemented in multiple embodiments separately or in anysuitable sub-combination.

A number of embodiments have been described. For example, the detaileddescription and the accompanying drawings to which it refers areintended to describe some, but not necessarily all, examples orembodiments of the system. The described embodiments are to beconsidered in all respects only as illustrative and not restrictive.Nevertheless, various modifications may be made without departing fromthe scope of the data processing system described herein. Accordingly,other embodiments are within the scope of the following claims.

Substantial variations may be made in accordance with specificrequirements. For example, customized hardware might also be used,and/or particular elements might be implemented in hardware, software(including portable software, such as applets, etc.), or both. Further,connection to other computing devices such as network input/outputdevices may be employed.

Information and signals may be represented using any of a variety ofdifferent technologies and techniques. For example, data, instructions,commands, information, signals, and symbols that may be referencedthroughout the above description may be represented by voltages,currents, electromagnetic waves, magnetic fields or particles, opticalfields or particles, or any combination thereof.

The methods, systems, and devices discussed above are examples. Variousalternative configurations may omit, substitute, or add variousprocedures or components as appropriate. Configurations may be describedas a process which is depicted as a flow diagram or block diagram.Although each may describe the operations as a sequential process, manyof the operations can be performed in parallel or concurrently. Inaddition, the order of the operations may be rearranged. A process mayhave additional stages not included in the figure. Specific details aregiven in the description to provide a thorough understanding of exampleconfigurations (including implementations). However, configurations maybe practiced without these specific details. For example, well-knowncircuits, processes, algorithms, structures, and techniques have beenshown without unnecessary detail in order to avoid obscuring theconfigurations. This description provides example configurations only,and does not limit the scope, applicability, or configurations of theclaims. Rather, the preceding description of the configurations willprovide those skilled in the art with an enabling description forimplementing described techniques. Various changes may be made in thefunction and arrangement of elements without departing from the scope ofthe disclosure.

Also, configurations may be described as a process which is depicted asa flow diagram or block diagram. Although each may describe theoperations as a sequential process, many of the operations can beperformed in parallel or concurrently. In addition, the order of theoperations may be rearranged. A process may have additional stages orfunctions not included in the figure. Furthermore, examples of themethods may be implemented by hardware, software, firmware, middleware,microcode, hardware description languages, or any combination thereof.When implemented in software, firmware, middleware, or microcode, theprogram code or code segments to perform the tasks may be stored in anon-transitory processor-readable medium such as a storage medium.Processors may perform the described tasks.

Components, functional or otherwise, shown in the figures and/ordiscussed herein as being connected or communicating with each other arecommunicatively coupled. That is, they may be directly or indirectlyconnected to enable communication between them.

As used herein, including in the claims, “and” as used in a list ofitems prefaced by “at least one of” indicates a disjunctive list suchthat, for example, a list of “at least one of A, B, and C” means A or Bor C or AB or AC or BC or ABC. (i.e., A and B and C), or combinationswith more than one feature (e.g., AA, AAB, ABBC, etc.). As used herein,including in the claims, unless otherwise stated, a statement that afunction or operation is “based on” an item or condition means that thefunction or operation is based on the stated item or condition and maybe based on one or more items and/or conditions in addition to thestated item or condition.

Having described several example configurations, various modifications,alternative constructions, and equivalents may be used without departingfrom the disclosure. For example, the above elements may be componentsof a larger system, wherein other rules may take precedence over orotherwise modify the application of the invention. Also, a number ofoperations may be undertaken before, during, or after the above elementsare considered. Also, technology evolves and, thus, many of the elementsare examples and do not bound the scope of the disclosure or claims.Accordingly, the above description does not bound the scope of theclaims. Further, more than one invention may be disclosed.

Other embodiments are within the scope of the invention. For example,due to the nature of software, functions described above can beimplemented using software, hardware, firmware, hardwiring, orcombinations of any of these. Features implementing functions may alsobe physically located at various locations, including being distributedsuch that portions of functions are implemented at different physicallocations.

The claims should not be read as limited to the described order orelements unless stated to that effect. It should be understood thatvarious changes in form and detail may be made by one of ordinary skillin the art without departing from the spirit and scope of the appendedclaims. All implementations that come within the spirit and scope of thefollowing claims and equivalents thereto are claimed.

1. A method for delivering gas-enriched blood within a vasculature of apatient, the method comprising: providing a gas-enrichment system thegas-enrichment system comprising a mixing chamber and a blood pump;inserting a catheter for drawing blood from the patient into a radialartery of the patient; drawing blood from the radial artery or from avessel upstream of the radial artery at a blood flow rate withoutcollapsing the artery or vessel to a degree that would substantiallyimpede drawing blood; generating a gas-enriched blood by mixingwithdrawn blood with a gas-enriched liquid in the mixing chamber; anddelivering the gas-enriched blood to the vasculature of the patient. 2.The method of claim 1, wherein the catheter is advanced to the vesselupstream of the radial artery and the blood is drawn from the vesselupstream of the radial artery.
 3. (canceled)
 4. The method of claim 1,wherein an inner diameter and a length of the catheter are sufficient tosupport a predetermined blood flow rate of 50-150 ml/min while avoidinga pressure drop that would cause pump cavitation.
 5. The method of claim4, wherein the inner diameter is 6-7 French, the length is 10 to 100 cm,and the pressure drop is from 0 mmHG to at least negative 50 mmHG. 6.The method of claim 1, wherein inserting the catheter into a radialartery of the patient comprises: accessing a subclavian artery of thepatient through the radial artery; and advancing the catheter into thesubclavian artery for drawing the blood from the subclavian artery.7.-9. (canceled)
 10. The method of claim 1, wherein inserting thecatheter into a radial artery of the patient comprises: advancing thecatheter into the radial artery of the patient until distal band on thecatheter alignment with a predetermined location in the vasculature ofthe patient.
 11. The method of claim 1, further comprising: controllinga draw rate of the catheter, wherein the controlling comprises:determining a maximum draw rate based on a size of the radial artery;determining a minimum draw rate and a draw pressure based on a pump flowrequirement of a pump configured to draw the blood from the radialartery; and controlling the draw rate to be between the maximum drawrate and the minimum draw rate. 12.-13. (canceled)
 14. The method ofclaim 11, wherein the minimum draw rate is 100 milliliters (ml) perminute and wherein the draw pressure is at least 50 millimeters perMercury (mmHg).
 15. The method of claim 11, further comprising:measuring the draw rate using a flow sensor; and generating an alert inresponse to measuring, by the flow sensor, that the draw rate is greaterthan the maximum draw rate or is less than the minimum draw rate. 16.The method of claim 11, further comprising: measuring the draw pressureusing a pressure sensor; and generating an alert in response tomeasuring, by the pressure sensor, that the draw pressure is greaterthan a maximum draw pressure. 17.-20. (canceled)
 21. The method of claim1, wherein the gas-enriched blood is formed in the mixing chamber bymixing the blood withdrawn from the patient with the gas-enriched liquidgenerated by a gas enrichment chamber. 22.-23. (canceled)
 24. The methodof claim 1, wherein the gas-enriched blood comprises a supersaturatedoxygen enriched blood.
 25. The method of claim 24, wherein thesupersaturated oxygen enriched blood comprises a supersaturated oxygenenriched blood having a pO2 of 600-1500 mmHg.
 26. The method of claim 1,further comprising: inserting a second catheter into a second radialartery of the patient for delivering the gas-enriched blood to thevasculature of the patient.
 27. The method of claim 1, furthercomprising: measuring a blood pressure in the radial artery or a vesselupstream of the radial artery using one or more pressure sensors,wherein a controller of the gas-enrichment system receives a signal fromthe one or more pressure sensors.
 28. The method of claim 27 wherein thecontroller generates an alert in response to receiving a signal from thepressure sensor indicating a blood pressure or change in blood pressurethat exceeds a threshold or is below a threshold.
 29. The method ofclaim 27, wherein the controller controls a pump to adjust a blood drawflow rate in response to receiving a signal from the pressure sensorindicating a blood pressure or change in blood pressure that exceeds athreshold or is below a threshold.
 30. (canceled)
 31. The method ofclaim 1, wherein drawing blood without collapsing the artery or vesselto a degree that would substantially impede drawing blood comprisespreventing a collapse that would result in more than 5-10% reduction incross-sectional area of an artery or vessel. 32.-33. (canceled)
 34. Asystem for delivering gas-enriched blood within a vasculature of apatient, the system comprising: a blood circuit, comprising: a pumpconfigured to circulate blood in the blood circuit; a mixing chamberconfigured to mix blood of the patient with a gas-enriched liquid toform a gas-enriched blood; a catheter; and a draw line coupled to themixing chamber and configured to connect the catheter to the mixingchamber; wherein the catheter is configured to be inserted into a radialartery of the patient, the catheter comprising one or more lumensconfigured to draw the blood from the radial artery or from a vesselupstream of the radial artery at a blood flow rate without collapsingthe artery or vessel to a degree that would substantially impede drawingblood and send the blood to the mixing chamber. 35.-104. (canceled) 105.The method of claim 1, wherein blood is drawn at a blood flow rate of10-500 mL/min and drawing blood without collapsing the artery or vesselto a degree that would substantially impede drawing blood comprisespreventing a reduction of blood flow over a threshold percentage ofabout 10-15%. 106.-107. (canceled)